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Klinger PH, Andrade AF, Delsin LE, et al.
Inhibition of SHH pathway mechanisms by arsenic trioxide in pediatric medulloblastomas: a comprehensive literature review.
Genet Mol Res. 2017; 16(1) [PubMed] Related Publications

Recent innovations in the genomic understanding of medulloblastomas have provided new ways to explore this highly invasive malignant brain cancer arising from the cerebellum. Among the four different medulloblastoma subgroups described to date, the sonic hedgehog (SHH) genetic pathway is the pathway activated in the tumorigenesis of medulloblastoma. SHH-related medulloblastomas are usually of nodular/desmoplastic histology and frequently occur in children under the age of three, an age group highly susceptible to the acute and long-term effects of treatment. Several new drugs aimed at SHH modulation are currently under development. This review focuses on the role of arsenic trioxide, a drug well established in clinical practice and probably an under-explored agent in medulloblastoma management, in the SHH pathway.

Related: Childhood Medulloblastoma / PNET Medulloblastoma Signal Transduction

Coca HA, Cebula H, Benmekhbi M, et al.
Diffuse intrinsic pontine gliomas in children: Interest of robotic frameless assisted biopsy. A technical note.
Neurochirurgie. 2016; 62(6):327-331 [PubMed] Related Publications

INTRODUCTION: Diffuse intrinsic pontine gliomas (DIPG) constitute 10-15% of all brain tumors in the pediatric population; currently prognosis remains poor, with an overall survival of 7-14 months. Recently the indication of DIPG biopsy has been enlarged due to the development of molecular biology and various ongoing clinical and therapeutic trials. Classically a biopsy is performed using a stereotactic frame assisted procedure but the workflow may sometimes be heavy and more complex especially in children. In this study the authors present their experience with frameless robotic-guided biopsy of DIPG in a pediatric population.
PATIENTS AND METHODS: Retrospective study on a series of five consecutive pediatric patients harboring DIPG treated over a 4-year period. All patients underwent frameless robotic-guided biopsy via a transcerebellar approach.
RESULTS: Among the 5 patients studied 3 were male and 2 female with a median age of 8.6 years [range 5 to 13 years]. Clinical presentation included ataxia, hemiparesis and cranial nerve palsy in all patients. MRI imaging of the lesion showed typical DIPG features (3 of them located in the pons) with hypo-intensity on T1 and hyper-intensity signal on T2 sequences and diffuse gadolinium enhancement. The mean procedure time was 56minutes (range 45 to 67minutes). No new postoperative neurological deficits were recorded. Histological diagnosis was achieved in all cases as follows: two anaplastic astrocytomas (grade III), two glioblastomas, and one diffuse astrocytoma (grade III).
CONCLUSION: Frameless robotic assisted biopsy of DIPG in pediatric population is an easier, effective, safe and highly accurate method to achieve diagnosis.

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Sánchez Fernández I, Loddenkemper T
Seizures caused by brain tumors in children.
Seizure. 2017; 44:98-107 [PubMed] Related Publications

PURPOSE: To review the epidemiology, clinical features, and treatment of seizures secondary to pediatric brain tumors.
METHOD: Literature review.
RESULTS: Pediatric brain tumors are the most common solid pediatric tumor and the most common cause of death in pediatric cancer. Seizures are one of the most common symptoms of pediatric brain tumors. Factors associated with increased risk of seizures include supratentorial location, gray matter involvement, low-grade, and certain histological features-especially dysembryoplastic neuroepithelial tumor, ganglioglioma, and oligodendroglioma. Leukemic infiltration of the brain, brain metastases of solid tumors, and brain injury secondary to chemotherapy or radiotherapy can also cause seizures. Mechanisms by which brain tumors cause seizures include metabolic, and neurotransmitter changes in peritumoral brain, morphologic changes - including malformation of cortical development - in peritumoral brain, and presence of peritumoral blood products, gliosis, and necrosis. As there is a high degree of uncertainty on how effective different antiepileptic drugs are for seizures caused by brain tumors, choices are often driven by the interaction and side effect profile. Classic antiepileptic drugs - phenobarbital, phenytoin, or carbamazepine - should be avoided as they may alter the metabolism of chemotherapeutic agents. Newer drugs - valproate, lamotrigine, topiramate, zonisamide, and levetiracetam - may be the preferred option in patients with tumors because of their very limited interaction with chemotherapy.
CONCLUSION: Seizures are a common presentation of pediatric brain tumors, especially in supratentorial tumors with gray matter involvement. Antiepileptic drug therapy is usually driven by the interaction and side effect profile and newer drugs with few interactions are generally preferred.

Bakhsheshian J, Jin DL, Chang KE, et al.
Risk factors associated with the surgical management of craniopharyngiomas in pediatric patients: analysis of 1961 patients from a national registry database.
Neurosurg Focus. 2016; 41(6):E8 [PubMed] Related Publications

OBJECTIVE Patient demographic characteristics, hospital volume, and admission status have been shown to impact surgical outcomes of sellar region tumors in adults; however, the data available following the resection of craniopharyngiomas in the pediatric population remain limited. The authors sought to identify potential risk factors associated with outcomes following surgical management of pediatric craniopharyngiomas. METHODS The Nationwide Inpatient Sample database and Kids' Inpatient Database were analyzed to include admissions for pediatric patients (≤ 18 years) who underwent a transcranial or transsphenoidal craniotomy for resection of a craniopharyngioma. Patient-level factors, including age, race, comorbidities, and insurance type, as well as hospital factors were collected. Outcomes analyzed included mortality rate, endocrine and nonendocrine complications, hospital charges, and length of stay. A multivariate model controlling for variables analyzed was constructed to examine significant independent risk factors. RESULTS Between 2000 and 2011, 1961 pediatric patients were identified who underwent a transcranial (71.2%) or a transsphenoidal (28.8%) craniotomy for resection of a craniopharyngioma. A major predilection for age was observed with the selection of a transcranial (23.4% in < 7-year-olds, 28.1% in 7- to 12-year-olds, and 19.7% in 13- to 18-year-olds) versus transphenoidal (2.9% in < 7-year-olds, 7.4% in 7- to 12-year-olds, and 18.4% in 13- to 18-year-olds) approach. No significant outcomes were associated with a particular surgical approach, except that 7- to 12-year-old patients had a higher risk of nonendocrine complications (relative risk [RR] 2.42, 95% CI 1.04-5.65, p = 0.04) with the transsphenoidal approach when compared with 13- to 18-year-old patients. The overall inpatient mortality rate was 0.5% and the most common postoperative complication was diabetes insipidus (64.2%). There were no independent factors associated with inpatient mortality rates and no significant differences in outcomes among groups based on sex and race. The average length of stay was 11.8 days, and the mean hospital charge was $116,5 22. Hospitals with medium and large bed capacity were protective against nonendocrine complications (RR 0.53, 95% CI 0.3-0.93, p = 0.03 [medium]; RR 0.45, 95% CI 0.25-0.8, p < 0.01 [large]) and total complications (RR 0.73, 95% CI 0.55-0.97, p = 0.03 [medium]; RR 0.68, 95% CI 0.51-0.9, p < 0.01 [large]) when compared with hospitals with small bed capacity (< 200 beds). Patients admitted to rural hospitals had an increased risk for nonendocrine complications (RR 2.56, 95% CI 1.11-5.9, p = 0.03). The presence of one or more medical comorbidities increased the risk of higher total complications (RR 1.38, 95% CI 1.14-1.68), p < 0.01 [1 comorbidity]; RR 2.37, 95% CI 1.98-2.84, p < 0.01 [≥ 2 comorbidities]) and higher total hospital charges (RR 2.9, 95% CI 1.08-7.81, p = 0.04 [1 comorbidity]; RR 9.1, 95% CI 3.74-22.12, p < 0.01 [≥ 2 comorbidities]). CONCLUSIONS This analysis identified patient age, comorbidities, insurance type, hospital bed capacity, and rural or nonteaching hospital status as independent risk factors for postoperative complications and/or increased hospital charges in pediatric patients with craniopharyngioma. Transsphenoidal surgery in younger patients with craniopharyngioma was a risk factor for nonendocrine complications.

Related: Childhood Craniopharyngioma Pituitary Tumors USA

Zhu X, McDowell MM, Newman WC, et al.
Severe cerebral edema following nivolumab treatment for pediatric glioblastoma: case report.
J Neurosurg Pediatr. 2017; 19(2):249-253 [PubMed] Related Publications

Nivolumab is an immune checkpoint inhibitor (ICI) currently undergoing Phase III clinical trials for the treatment of glioblastoma. The authors present the case of a 10-year-old girl with glioblastoma treated with nivolumab under compassionate-use guidelines. After the first dose of nivolumab the patient developed hemiparesis, cerebral edema, and significant midline shift due to severe tumor necrosis. She was managed using intravenous dexamethasone and discharged on a dexamethasone taper. The patient's condition rapidly deteriorated after the second dose of nivolumab, demonstrating hemiplegia, seizures, and eventually unresponsiveness with a fixed and dilated left pupil. Computed tomography of her brain revealed malignant cerebral edema requiring emergency decompressive hemicraniectomy. Repeat imaging demonstrated increased size of the lesion, reflecting immune-mediated inflammation and tumor necrosis. The patient remained densely hemiplegic, but became progressively more interactive and was ultimately extubated. She resumed nivolumab several weeks later, but again her condition deteriorated with headache, vomiting, swelling at the craniectomy site, and limited right-sided facial movement following the sixth dose. MRI demonstrated severe midline shift and uncal herniation despite her craniectomy. Her condition gradually declined, and she died several days later under "do not resuscitate/do not intubate" orders. To the authors' knowledge, this represents the first case of malignant cerebral edema requiring operative intervention following nivolumab treatment for glioblastoma in a pediatric patient.

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Yu J, Li H
The expression of FAT1 is associated with overall survival in children with medulloblastoma.
Tumori. 2017; 103(1):44-52 [PubMed] Related Publications

PURPOSE: The FAT1 gene is involved in some cancers; however, its role in medulloblastoma is less clear. This study investigated the effects of FAT1 expression on the prognosis of medulloblastoma patients.
METHODS: Whole exome sequencing was undertaken in 40 medulloblastoma patient samples. FAT1 mRNA and protein expression levels in normal and brain tumor tissues were determined by fluorescence quantitative PCR and immunohistochemistry, respectively. The association of FAT1 expression with overall survival (OS) was examined by Kaplan-Meier curve analysis with a log-rank test. Following lentiviral-mediated FAT1 knockdown using shRNA in Daoy cells, proliferation, Wnt signaling, and β-catenin protein expression were determined.
RESULTS: Eight FAT1 missense mutations were detected in 7 patients. FAT1 mRNA expression in tumors was significantly lower than in adjacent normal tissue (p = 0.043). The OS of patients with high FAT1 protein expression was significantly longer than that of patients with low FAT1 protein expression (median survival time: 24.3 vs 4.8 months, respectively; p = 0.002). shFAT1 cells had significantly higher proliferation rates than shControl cells (p≤0.028). Furthermore, the mRNA expression of LEF1, β-catenin, and cyclin D1 was significantly upregulated in shFAT1-Daoy cells (p≤0.018).
CONCLUSIONS: Low FAT1 expression was associated with poor prognosis in children with medulloblastoma. Furthermore, FAT1 may act on Wnt signaling pathway to exert its antitumor effect.

Related: Childhood Medulloblastoma / PNET Medulloblastoma Signal Transduction CTNNB1 FAT1

Smith H, Taplin A, Syed S, Adamo MA
Correlation between intraoperative ultrasound and postoperative MRI in pediatric tumor surgery.
J Neurosurg Pediatr. 2016; 18(5):578-584 [PubMed] Related Publications

OBJECTIVE Malignant disease of the CNS is the primary etiology for deaths resulting from cancer in the pediatric population. It has been well documented that outcomes of pediatric neurosurgery rely on the extent of tumor resection. Therefore, techniques that improve surgical results have significant clinical implications. Intraoperative ultrasound (IOUS) offers real-time surgical guidance and a more accurate means for detecting residual tumor that is inconspicuous to the naked eye. The objective of this study was to evaluate the correlation of extent of resection between IOUS and postoperative MRI. The authors measured the correlation of extent of resection, negative predictive value, and sensitivity of IOUS and compared them with those of MRI. METHODS This study consisted of a retrospective review of the medical charts of all pediatric patients who underwent neurosurgical treatment of a tumor between August 2009 and July 2015 at Albany Medical Center. Included were patients who were aged ≤ 21 years, who underwent brain or spinal tumor resection, for whom IOUS was used during the tumor resection, and for whom postoperative MRI (with and without contrast) was performed within 1 week of surgery. RESULTS Sixty-two patients met inclusion criteria for the study (33 males, mean age 10.0 years). The IOUS results very significantly correlated with postoperative MRI results (φ = 0.726; p = 0.000000011; negative predictive value 86.3% [95% CI 73.7%-94.3%]). These results exemplify a 71% overall gross-total resection rate and 80% intended gross-total resection rate with the use of IOUS (i.e., excluding cases performed only for debulking purposes). CONCLUSIONS The use of IOUS may play an important role in achieving a greater extent of resection by providing real-time information on tumor volume and location in the setting of brain shift throughout the course of an operation. The authors support the use of IOUS in pediatric CNS tumor surgery to improve clinical outcomes at low cost with minimal additional operating-room time and no identified additional risk.

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Giordano M, Samii A, Lawson McLean AC, et al.
Intraoperative magnetic resonance imaging in pediatric neurosurgery: safety and utility.
J Neurosurg Pediatr. 2017; 19(1):77-84 [PubMed] Related Publications

OBJECTIVE The use of high-field intraoperative MRI has been largely studied for the treatment of intracranial tumors in adult patients. In this study, the authors investigated the safety, advantages, and limitations of high-field iMRI for cranial neurosurgical procedures in pediatric patients, with particular attention to craniopharyngiomas and gliomas. METHODS The authors performed 82 surgical procedures in patients under 16 years of age (range 0.8-15 years) over an 8-year period (2007-2014) using iMRI. The population was divided into 3 groups based on the condition treated: sellar region tumors (Group 1), gliomas (Group 2), and other pathological entities (Group 3). The patients' pre- and postoperative neurological status, the presence of residual tumor, the number of intraoperative scans, and complications were evaluated. RESULTS In Group 1, gross-total resection (GTR) was performed in 22 (88%) of the procedures and subtotal resection (STR) in 3 (12%). In Group 2, GTR, STR, and partial resection (PR) were performed, respectively, in 15 (56%), 7 (26%), and 5 (18%) of the procedures. In Group 3, GTR was performed in 28 (93%) and STR in 2 (7%) of the procedures. In cases of craniopharyngioma (Group 1) and glioma (Group 2) in which a complete removal was planned, iMRI allowed localization of residual lesions and attainment of the surgical goal through further resection, respectively, in 18% and 27% of the procedures. Moreover, in gliomas the resection could be extended from partial to subtotal in 50% of the cases. In 17% of the patients in Group 3, iMRI enabled the identification and further removal of tumor remnants. There was no intra- or postoperative complication related to the use of iMRI despite special technical difficulties in smaller children. CONCLUSIONS In this study, the use of iMRI in children proved to be safe. It was most effective in increasing the extent of tumor resection, especially in patients with low-grade gliomas and craniopharyngiomas. The most prominent disadvantage of high-field iMRI was the limitation with respect to operative positioning due to the configuration of the surgical table.

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Liu J, Keisling MP, Samkari A, et al.
Malignant glioma with primitive neuroectodermal tumor-like component (MG-PNET): novel microarray findings in a pediatric patient.
Clin Neuropathol. 2016 Nov/Dec; 35(6):353-367 [PubMed] Related Publications

Central nervous system (CNS) tumors exhibiting dual features of malignant glioma (MG) and primitive neuroectodermal tumor (PNET) are rare and diagnostically challenging. Previous studies have shown that MG-PNET carry MYCN or MYC gene amplifications within the PNET component concomitant with glioma-associated alterations, most commonly 10q loss, in both components [9]. Here we confirm and extend the profile of molecular genetic findings in a MG-PNET involving the left frontal lobe of a 12-year-old male. Histologically, the PNET-like component showed morphological features akin to anaplastic medulloblastoma highlighted by widespread immunoreactivity for βIII-tubulin (TUBB3) and nonphosphorylated neurofilament protein, and to a lesser degree, Neu-N, synaptophysin, and CD99, whereas the gliomatous component was demarcated by glial fibrillary acidic protein (GFAP) labeling. Immunohistochemical labeling with an anti-H3K27M mutant-specific antibody was not detectable in either gliomatous and/or PNET-like areas. Interphase fluorescent in situ hybridization (FISH) study on touch preparations from frozen tumor and formaldehyde-fixed, paraffin-embedded histological sections showed amplification of MYC in both PNET-like and gliomatous areas. Single nucleotide polymorphism (SNP) microarray analysis revealed that the tumor carried gains of multiple chromosomes and chromosome arms, losses of multiple chromosomes and chromosome arms, gains of multiple chromosomal segments (not limited to amplification of chromosomal segments 4q12 including PDGFRA, and 8q24.21 including MYC), and a hitherto unreported chromothripsis-like abnormality on chromosome 8. No mutations were identified for IDH1, IDH2, or BRAF genes by sequence analysis. The molecular genetic findings support the presence of a CNS-PNET as an integral part of the tumor coupled with overlapping genetic alterations found in both adult and pediatric high-grade gliomas/glioblastoma. Collectively, microarray data point to a complex underpinning of genetic alterations associated with the MG-PNET tumor phenotype.
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Tovar-Spinoza Z, Choi H
MRI-guided laser interstitial thermal therapy for the treatment of low-grade gliomas in children: a case-series review, description of the current technologies and perspectives.
Childs Nerv Syst. 2016; 32(10):1947-56 [PubMed] Related Publications

BACKGROUND: Pediatric low-grade gliomas (LGGs) account for approximately half of all pediatric central nervous system tumors. The low-grade gliomas' first line of treatment is gross total resection. However, when gross total resection is not possible, options for adjuvant therapy are limited. MRI-guided laser ablation (magnetic resonance-guided laser interstitial thermal therapy (MRgLITT)) offers a new option for treatment in selected cases. We present a description of the current MRgLITT technology and an exemplary case-series review of our experience in its use in LGGs.
CASE DESCRIPTION: A 19-month-old male was referred to the pediatric neurosurgery clinic with an incidental left temporal lesion discovered on a prenatal ultrasound. An MRI of the brain revealed a diffuse mesial temporal lesion. Electroencephalogram (EEG) showed generalized activity arising from the lesion. The patient underwent a navigation-guided biopsy then, two bolts were secured to the skull, and laser ablation was performed with intraoperative MR guidance. Pathology was consistent with ganglioglioma. Follow-up images 13 months after ablation showed a significant volumetric reduction in size of the tumor.
DISCUSSION: It is important to achieve maximal resection of low-grade gliomas in children, lessening the need for adjuvant chemotherapy and radiotherapy, while minimizing the length of hospital stay and disruption to the child's life. Of our nine LGGs patients treated with this technology, six had undergone previous surgery and MRgLITT proved itself to be a safe surgical treatment option to achieve further cytoreduction. While most of the cases are pilocytic astrocytomas, the location of the tumors was surgically challenging. Eight of the nine cases required a single trajectory-laser-while our case example requires two lasers. Only a case of a midbrain-thalamic tumor presented a post-ablation significant brain edema as perioperative complication [1]. Eight of the nine tumors did not require any coadjuvant therapy or further surgical treatment to date.
CONCLUSION: MRIgLITT is a successful option for treatment for selected de novo or recurrent low-grade gliomas in children. It can be combined with other therapies offering the advantages of a minimally invasive procedure. LITT may be added to the current pediatric neuro-oncology protocols, but larger prospective series are needed to show the effectiveness of LITT and to standardize indications and protocols.

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Fernández MB, Alonso VP
Conventional chemotherapy and perspectives for molecular-based oncological treatment in pediatric hemispheric low-grade gliomas.
Childs Nerv Syst. 2016; 32(10):1939-45 [PubMed] Related Publications

INTRODUCTION: Pediatric low-grade gliomas (PLGG) are the most common primary central nervous system tumor in children. Patients in whom gross total resection can be achieved have an excellent overall (OS) and event-free survival (EFS) and do not require adjuvant therapy. However, children with unresectable tumors often experience multiple progressions and require additional treatment.
CONVENTIONAL CHEMOTHERAPY: Radiotherapy results in long-term tumor control, but it is associated with significant toxicity, making chemotherapy the preferred therapeutic option. Several chemotherapy combinations have been found to be successful in PLGG, but 5-year EFS has been below 60 % with most of them.
MOLECULAR-BASED TREATMENT: Recent molecular advances have led to a better understanding of the molecular pathways involved in the biology of LGG, allowing the development of promising tumor-specific, molecularly targeted therapies.

Related: Signal Transduction MTOR

Chieffo D, Tamburrini G, Frassanito P, et al.
Preoperative neurocognitive evaluation as a predictor of brain tumor grading in pediatric patients with supratentorial hemispheric tumors.
Childs Nerv Syst. 2016; 32(10):1931-7 [PubMed] Related Publications

OBJECTIVE: The objective of the present study was to retrospectively evaluate the relationship between tumor grading and a selective evaluation of neurocognitive and behavioral functions in children with supratentorial hemispheric brain tumors.
METHODS: Children admitted with a diagnosis of supratentorial hemispheric tumors involving the cerebral hemispheres or the thalamus at the Pediatric Neurosurgery Unit of the Catholic University of Rome between January 2008 and January 2014 were considered for the present study. Exclusion criteria were represented by age less than 2 years, severe neurological deficits, seizures, and a metastatic disease. A selective neurocognitive and behavioral workout was used for children aged less and more than 5 years.
RESULTS: Global cognitive functions as well as selective neurocognitive and behavioral profiles were found to be significantly worse in children with low-grade tumors, compared with those affected by higher-grades histotypes. Frontal locations for cortical tumors and thalamic lesions were significantly related with worse results, with a clear contribution of dominant vs. nondominant hemisphere involvement and an age higher than 5 years.
CONCLUSIONS: Preoperative global and selective neurocognitive evaluation might contribute to the prediction of the tumor aggressiveness. Due to a longer clinical history, more benign tumors more frequently arrive to the diagnosis with a neurocognitive compromise in spite of an apparently mild presence of neurological symptoms and signs.

Brown MT, Boop FA
Epilepsy surgery for pediatric low-grade gliomas of the cerebral hemispheres: neurosurgical considerations and outcomes.
Childs Nerv Syst. 2016; 32(10):1923-30 [PubMed] Related Publications

INTRODUCTION: Pediatric low-grade tumors are found in roughly 1-3 % of patients with childhood epilepsy; seizures associated with these tumors are often medically refractory and often present a significant morbidity, greater than the presence of the tumor itself.
DISCUSSION: The unique morbidity of the seizures often requires an epilepsy surgical approach over a standard oncologic resection to achieve a reduction in morbidity for the child. Multiple quality-of-life studies have shown that unless a patient is seizure-free, they remain disabled throughout their life; the best way to achieve this in our patient population is with a multidisciplinary team approach with treatment goals focusing primarily on the epilepsy.
CONCLUSION: In those patients treated with gross total resection, roughly 80 % will have an Engel class I outcome and 90 % will achieve some reduction in seizure frequency with a significant improvement in quality of life.

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Giordano M, Arraez C, Samii A, et al.
Neurosurgical tools to extend tumor resection in pediatric hemispheric low-grade gliomas: iMRI.
Childs Nerv Syst. 2016; 32(10):1915-22 [PubMed] Related Publications

INTRODUCTION: The treatment of low-grade gliomas (LGGs) in pediatric age is still controversial. However, most authors report longer life expectancy in case of completely removed cerebral gliomas. Intraoperative magnetic resonance imaging (iMRI) is increasingly utilized in the surgical management of intra-axial tumor in adults following the demonstration of its effectiveness. In this article, we analyze the management of LGG using iMRI focusing on its impact on resection rate and its limits in the pediatric population.
METHODS: We performed review of the literature regarding the treatment of LGG using iMRI focusing on its impact on resection rate and its limits in the pediatric population. Some exemplary cases are also described.
RESULTS: Intraoperative MRI allowed extension of tumor resection after the depiction of residual tumor at the intraoperative imaging control from 21 to 52 % of the cases in the published series. Moreover, the early reoperation rate was significantly lower when compared with the population treated without this tool (0 % vs 7-14 %). Some technical difficulties have been described in literature regarding the use of iMRI in the pediatric population especially for positioning due to the structure of the headrest coil designed for adult patients.
CONCLUSION: The analysis of the literature and our own experience with iMRI in children indicates significant advantages in the resection of LGG offered by the technique. All these advantages are obtained without elongation of the surgical times or increased risk for complications, namely infection. The main limit for a wider diffusion of iMRI for the pediatric neurosurgical center is the cost required, for acquisition of the system, especially for high-field magnet, and the environmental and organizational changes necessary for its use.

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Coppola A, Tramontano V, Basaldella F, et al.
Intra-operative neurophysiological mapping and monitoring during brain tumour surgery in children: an update.
Childs Nerv Syst. 2016; 32(10):1849-59 [PubMed] Related Publications

INTRODUCTION: Over the past decade, the reluctance to operate in eloquent brain areas has been reconsidered in the light of the advent of new peri-operative functional neuroimaging techniques and new evidence from neuro-oncology. To maximise tumour resection while minimising morbidity should be the goal of brain surgery in children as much as it is in adults, and preservation of brain functions is critical in the light of the increased survival and the expectations in terms of quality of life.
DISCUSSION: Intra-operative neurophysiology is the gold standard to localise and preserve brain functions during surgery and is increasingly used in paediatric neurosurgery. Yet, the developing nervous system has peculiar characteristics in terms of anatomical and physiological maturation, and some technical aspects need to be tailored for its use in children, especially in infants. This paper will review the most recent advances in the field of intra-operative neurophysiology (ION) techniques during brain surgery, focussing on those aspects that are relevant to the paediatric neurosurgery practice.

Tomita T, Volk JM, Shen W, Pundy T
Glioneuronal tumors of cerebral hemisphere in children: correlation of surgical resection with seizure outcomes and tumor recurrences.
Childs Nerv Syst. 2016; 32(10):1839-48 [PubMed] Related Publications

OBJECT: Glioneuronal tumors are common neoplasms among the cerebral hemisphere during childhood. They consist of several histological types, of which gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumors (DNTs) are most common and often present with seizures. A great majority of glioneuronal tumors are benign. However, there are conflict reports regarding postoperative tumor recurrence rates and seizure control. The authors analyzed and compared these tumors for their locations and histology and the tumor and seizure control following resection.
METHODS: The authors conducted a retrospective analysis of patients with pediatric glioneuronal tumors in the cerebral hemisphere. All histology reports and neuroimaging are reviewed. Seizure group and non-seizure group were compared with their tumor types and locations. The extent of tumor resections were divided into gross total resection (GTR) and subtotal resection (STR). Postoperative tumor recurrence-free survival (RFS) and seizure-free survival for patients who had the initial surgery done at our institution were calculated using Kaplan-Meier method.
RESULTS: There were 90 glioneuronal tumors including 58 GGs, 22 DNTs, 3 papillary glioneuronal tumor, 3 desmoplastic infantile gangliogliomas, 3 anaplastic GGs, and 1 central neurocytoma. Seventy-one patients (seizure group) presented with seizures. The temporal lobe is the most common location, 50 % in this series. GTR was attained in 79 patients and STR in 11. All of the patients with GTR had lesionectomy, and only six of them had extended corticectomy or partial lobectomy. Postoperative seizure outcome showed that 64 (90 %) of seizure group had Engel's class I, but five patients subsequently developed recurrent seizures. Patients with DNTs had a higher seizure recurrence rate. Tumor RFS was 87 % at 5 years and 75.5 % at 10 years. There are no significant difference in tumor recurrences between GGs and DNTs (p = 0.876). Comparison between GRT (67) and STR (9) showed that in spite of the better 5-year tumor RFSs among GRT group (94 %) than STR group (66 %), the 10-year RFSs showed no significant difference between GRT and STR groups (p = 0.719). Recurrent seizures are often related to recurrent tumor.
CONCLUSION: Lesionectomy alone often provides a high-rate seizure freedom. GGs and DNTs are benign tumor, but recurrences of GGs and DNTs are not uncommon. They may show late recurrences in spite of GTR. These patients need longer follow-up for 10 years. Recurrent seizures are often related to a tumor recurrence.

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Juhász C, Bosnyák E
PET and SPECT studies in children with hemispheric low-grade gliomas.
Childs Nerv Syst. 2016; 32(10):1823-32 [PubMed] Article available free on PMC after 01/10/2017 Related Publications

Molecular imaging is playing an increasing role in the pretreatment evaluation of low-grade gliomas. While glucose positron emission tomography (PET) can be helpful to differentiate low-grade from high-grade tumors, PET imaging with amino acid radiotracers has several advantages, such as better differentiation between tumors and non-tumorous lesions, optimized biopsy targeting, and improved detection of tumor recurrence. This review provides a brief overview of single-photon emission computed tomography (SPECT) studies followed by a more detailed review of the clinical applications of glucose and amino acid PET imaging in low-grade hemispheric gliomas. We discuss key differences in the performance of the most commonly utilized PET radiotracers and highlight the advantage of PET/MRI fusion to obtain optimal information about tumor extent, heterogeneity, and metabolism. Recent data also suggest that simultaneous acquisition of PET/MR images and the combination of advanced MRI techniques with quantitative PET can further improve the pretreatment and post-treatment evaluation of pediatric brain tumors.

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Gaudino S, Russo R, Verdolotti T, et al.
Advanced MR imaging in hemispheric low-grade gliomas before surgery; the indications and limits in the pediatric age.
Childs Nerv Syst. 2016; 32(10):1813-22 [PubMed] Related Publications

INTRODUCTION: Advanced magnetic resonance imaging (MRI) techniques is an umbrella term that includes diffusion (DWI) and diffusion tensor (DTI), perfusion (PWI), spectroscopy (MRS), and functional (fMRI) imaging. These advanced modalities have improved the imaging of brain tumors and provided valuable additional information for treatment planning. Despite abundant literature on advanced MRI techniques in adult brain tumors, few reports exist for pediatric brain ones, potentially because of technical challenges.
REVIEW OF THE LITERATURE: The authors review techniques and clinical applications of DWI, PWI, MRS, and fMRI, in the setting of pediatric hemispheric low-grade gliomas.
PERSONAL EXPERIENCE: The authors propose their personal experience to highlight benefits and limits of advanced MR imaging in diagnosis, grading, and presurgical planning of pediatric hemispheric low-grade gliomas.
DISCUSSION: Advanced techniques should be used as complementary tools to conventional MRI, and in theory, the combined use of the three techniques should ensure achieving the best results in the diagnosis of hemispheric low-grade glioma and in presurgical planning to maximize tumor resection and preserve brain function.
FUTURE PERSPECTIVES: In the setting of pediatric neurooncology, these techniques can be used to distinguish low-grade from high-grade tumor. However, these methods have to be applied on a large scale to understand their real potential and clinical relapse, and further technical development is required to reduce the excessive scan times and other technical limitations.

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Raybaud C
Cerebral hemispheric low-grade glial tumors in children: preoperative anatomic assessment with MRI and DTI.
Childs Nerv Syst. 2016; 32(10):1799-811 [PubMed] Related Publications

PURPOSE: The aims of this study are to analyze how the nature and the behavior of low-grade glial tumors (LGGT) in children may correlate with the anatomy of the cerebral hemispheres and to evaluate the consequent impact of diffusion tensor imaging (DTI) techniques in the presurgical assessment.
METHODS: This is a combined review of a series of 155 cases of LGGT and of the recent literature on the subject.
RESULTS: The cases retrieved from our data bank were divided in central hemispheric tumors (basal ganglia and thalami) (36 cases), glioneuronal cortical-based tumors (49 cases), and glial tumors of the cerebral mantle (70 cases). A close correlation was found in the thalamus between the primary location of the tumor (juxta-ventricular, inferior, lateral, bilateral) and its extension (ventricular lumen, midbrain and mesial temporal, globus pallidus, respectively) which may relate to the connectivity. Among the glioneuronal tumors, most gangliogliomas were located in the temporal lobe and especially in the mesial temporal structures. In addition, the morphologic feature of the ganglioglioma was different there from the neocortical areas. As a complementary approach, DTI data may assist in evaluating the structure and the extension of the LGGT, in addition to planning the surgical strategy.
CONCLUSIONS: In the cerebral hemispheres like in the rest of the central nervous system, there is some degree of correlation between the anatomy and the nature, appearance, and behavior of the LGGT in children.

Lassaletta A, Zapotocky M, Bouffet E, et al.
An integrative molecular and genomic analysis of pediatric hemispheric low-grade gliomas: an update.
Childs Nerv Syst. 2016; 32(10):1789-97 [PubMed] Related Publications

Hemispheric low-grade gliomas account for the second most common location in pediatric low-grade gliomas (PLGGs) after the cerebellum. The pathological spectrum includes gangliogliomas, dysembryoplastic neuroepithelial tumors (DNETs), diffuse astrocytomas, pilocytic astrocytomas, and pleomorphic xanthoastrocytomas (PXAs), among others. Clinically, hemispheric PLGGs represent a well-recognized cause of intractable epilepsy in children and adolescents. With an excellent long-term outcome, surgery remains the cornerstone and patients with gross total resection typically do not need any further therapies. The recent literature about hemispheric PLGGs was reviewed to provide an up-to-date overview of the molecular and cell biology of these tumors. Hemispheric PLGGs can harbor multiple alterations involving BRAFV600E, FGFR, NTRK, MYB/MYBL1, IDH, and BRAF-KIAA1549 fusions. However, the clinical significance of most of these alterations is still to be defined. The role of RAS/MAPK mutations and other alterations in hemispheric PLGGs is of interest from diagnostic, prognostic, and therapeutic perspectives. Molecular testing for these tumors should be encouraged, since the findings can have an important impact not only in prognosis but also in therapeutic strategies.

Related: Childhood Brain Tumours Childhood Brain Tumors Brain Stem Glioma - Childhood BRAF FGFR1 ALK

Chen S, Gu S, Wang Y, et al.
Exposure to pyrethroid pesticides and the risk of childhood brain tumors in East China.
Environ Pollut. 2016; 218:1128-1134 [PubMed] Related Publications

Pesticide exposure is hypothesized as one of the risk factors for the development of childhood brain tumors (CBT). This hospital-based case-control study evaluated the association of pyrethroid pesticide exposure with the risk for CBT in a children population in East China. In total, 161 CBT cases and 170 controls were recruited from 2 children's medical centers in Shanghai (Xinhua Hospital and Shanghai Children's Medical Center) between September 2012 and June 2015. The cases and controls were matched for age, sex, and province of residence. Pyrethroid pesticide exposure was evaluated by urinalysis of 3 nonspecific metabolites of pyrethroids (cis-DCCA, trans-DCCA, and 3-PBA) using gas chromatography-mass spectrometry (GC-MS) detection and by administering a questionnaire. Unconditional logistic regression showed that trans-DCCA, 3-PBA, and total metabolites (sum of the 3 metabolites) were positively associated with the increased risk of CBT. Children in the highest quartile had a nearly 3-fold increased risk of CBT compared with those in the lowest quartile after adjusting for confounding factors (trans-DCCA, odds ratio (OR) = 2.58, 95% confidence interval (CI), 1.38-4.80, p = 0.003; 3-PBA, OR = 3.26, 95% CI, 1.73-6.14, p < 0.0001; total metabolites, OR = 3.60, 95% CI, 1.87-6.93, p < 0.0001). We also found that exposure to both mosquitocide and cockroach killer was related to the increased risk of CBT (mosquitocide, OR = 1.68, 95% CI, 1.06-2.67, p = 0.027; cockroach killer, OR = 1.83, 95% CI, 1.13-2.95, p = 0.013). These findings indicate that exposure to pyrethroid pesticides might be associated with increased risk of CBT. Prospective cohort studies with larger sample sizes are required to confirm this conclusion.

Related: Childhood Brain Tumours Childhood Brain Tumors

Tuntapakul S, Kitkhuandee A, Kanpittaya J, et al.
Pineal calcification is associated with pediatric primary brain tumor.
Asia Pac J Clin Oncol. 2016; 12(4):e405-e410 [PubMed] Related Publications

AIM: Melatonin has been associated with various tumors, including brain tumor, and shown to inhibit growth of neuroblastoma cells and gliomas in animal models. Likewise, patients with glioblastoma receiving melatonin reported better survival than controls. Pineal calcification may lead to a decreased production of melatonin by calcified glands. This study assessed association between pineal calcification and primary brain tumor in pediatric/adolescent patients.
METHODS: Medical chart review was conducted in 181 patients <15 years old who had undergone brain computed tomography (CT) during 2008-2012. Pineal calcification was identified using brain CT scan by an experienced neurosurgeon. Primary brain tumor was confirmed by CT scan and histology, and association with pineal calcification was estimated using multiple logistic regression, adjusted for age and gender.
RESULTS: Primary brain tumor was detected in 51 patients (mean age 9.0, standard deviation 4.0 years), with medulloblastoma being the most common (11 patients). Pineal calcification was detected in 12 patients (23.5%) with primary brain tumor, while only 11 patients (8.5%) without tumor had pineal calcification. Adjusted for patients' ages and genders, pineal calcification was associated with an increase in primary brain tumor of 2.82-fold (odds ratio 2.82; 95% confidence interval 1.12-7.08, P = 0.027).
CONCLUSION: Pineal calcification appears to be associated with primary brain tumor. Further studies to explore this link are discussed and warranted.

Related: Childhood Brain Tumours Childhood Brain Tumors

Chan V, Pole JD, Keightley M, et al.
Children and youth with non-traumatic brain injury: a population based perspective.
BMC Neurol. 2016; 16:110 [PubMed] Article available free on PMC after 01/10/2017 Related Publications

BACKGROUND: Children and youth with non-traumatic brain injury (nTBI) are often overlooked in regard to the need for post-injury health services. This study provided population-based data on their burden on healthcare services, including data by subtypes of nTBI, to provide the foundation for future research to inform resource allocation and healthcare planning for this population.
METHODS: A retrospective cohort study design was used. Children and youth with nTBI in population-based healthcare data were identified using International Classification of Diseases Version 10 codes. The rate of nTBI episodes of care, demographic and clinical characteristics, and discharge destinations from acute care and by type of nTBI were identified.
RESULTS: The rate of pediatric nTBI episodes of care was 82.3 per 100,000 (N = 17,977); the average stay in acute care was 13.4 days (SD = 25.6 days) and 35% were in intensive care units. Approximately 15% were transferred to another inpatient setting and 6% died in acute care. By subtypes of nTBI, the highest rates were among those with a diagnosis of toxic effect of substances (22.7 per 100,000), brain tumours (18.4 per 100,000), and meningitis (15.4 per 100,000). Clinical characteristics and discharge destinations from the acute care setting varied by subtype of nTBI; the proportion of patients that spent at least one day in intensive care units and the proportion discharged home ranged from 25.9% to 58.2% and from 50.6% to 76.4%, respectively.
CONCLUSIONS: Children and youth with nTBI currently put an increased demand on the healthcare system. Active surveillance of and in-depth research on nTBI, including subtypes of nTBI, is needed to ensure that timely, appropriate, and targeted care is available for this pediatric population.

Related: Childhood Brain Tumours Childhood Brain Tumors

Zhang S, Fang Y, Cai BW, et al.
Intracystic bleomycin for cystic craniopharyngiomas in children.
Cochrane Database Syst Rev. 2016; 7:CD008890 [PubMed] Related Publications

BACKGROUND: Craniopharyngiomas are the most common benign histological tumours to involve the hypothalamo-pituitary region in childhood. Cystic craniopharyngiomas account for more than 90% of the tumours. The optimal treatment of cystic craniopharyngioma remains controversial. Radical resection is the treatment of choice in patients with favourable tumour localisation. When the tumour localisation is unfavourable, a gross-total or partial resection followed by radiotherapy is the main treatment option in adults. However, it presents a risk of morbidity, especially for children. Intracystic bleomycin has been utilised potentially to delay the use of radiotherapy or radical resection, to decrease morbidity. This review is the second update of a previously published Cochrane review.
OBJECTIVES: To assess the benefits and harmful effects of intracystic bleomycin in children from birth to 18 years with cystic craniopharyngioma when compared to placebo (no treatment), surgical treatment (with or without adjuvant radiotherapy) or other intracystic treatments.
SEARCH METHODS: We searched the electronic databases CENTRAL (2016, Issue 1), MEDLINE/PubMed (from 1966 to February 2016) and EMBASE/Ovid (from 1980 to February 2016) with pre-specified terms. In addition, we searched the reference lists of relevant articles and reviews, conference proceedings (International Society for Paediatric Oncology 2005-2015) and ongoing trial databases (Register of the National Institute of Health and International Standard Randomised Controlled Trial Number (ISRCTN) register) in February 2016.
SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-randomised trials or controlled clinical trials (CCTs) comparing intracystic bleomycin and other treatments for cystic craniopharyngiomas in children (from birth to 18 years).
DATA COLLECTION AND ANALYSIS: Two review authors independently performed the study selection, data extraction and 'Risk of bias' assessment. We used risk ratio (RR) for binary data and mean difference (MD) for continuous data. If one of the treatment groups experienced no events and there was only one study available for the outcome, we used the Fischer's exact test. We performed analysis according to the guidelines in the Cochrane Handbook for Systematic reviews of Interventions.
MAIN RESULTS: We could not identify any studies in which the only difference between the treatment groups was the use of intracystic bleomycin. We did identify a RCT comparing intracystic bleomycin with intracystic phosphorus(32) ((32)P) (seven children). In this update we identified no additional studies. The included study had a high risk of bias. Survival could not be evaluated. There was no clear evidence of a difference between the treatment groups in cyst reduction (MD -0.15, 95% confidence interval (CI) -0.69 to 0.39, P value = 0.59, very low quality of evidence), neurological status (Fisher's exact P value = 0.429, very low quality of evidence), third nerve paralysis (Fischer's exact P value = 1.00, very low quality of evidence), fever (RR 2.92, 95% CI 0.73 to 11.70, P value = 0.13, very low quality of evidence) or total adverse effects (RR 1.75, 95% CI 0.68 to 4.53, P value = 0.25, very low quality of evidence). There was a significant difference in favour of the (32)P group for the occurrence of headache and vomiting (Fischer's exact P value = 0.029, very low quality of evidence for both outcomes).
AUTHORS' CONCLUSIONS: Since we identified no RCTs, quasi-randomised trials or CCTs of the treatment of cystic craniopharyngiomas in children in which only the use of intracystic bleomycin differed between the treatment groups, no definitive conclusions could be made about the effects of intracystic bleomycin in these patients. Only one low-power RCT comparing intracystic bleomycin with intracystic (32)P treatment was available, but no definitive conclusions can be made about the effectiveness of these agents in children with cystic craniopharyngiomas. Based on the currently available evidence, we are not able to give recommendations for the use of intracystic bleomycin in the treatment of cystic craniopharyngiomas in children. High-quality RCTs are needed.

Related: Bleomycin Childhood Craniopharyngioma Pituitary Tumors

Gokce-Samar Z, Beuriat PA, Faure-Conter C, et al.
Pre-radiation chemotherapy improves survival in pediatric diffuse intrinsic pontine gliomas.
Childs Nerv Syst. 2016; 32(8):1415-23 [PubMed] Related Publications

BACKGROUND: The median survival of patients with diffuse intrinsic pontine glioma (DIPG) remains less than 1 year. The BSG 98 pre-irradiation chemotherapy protocol showed a significant increase in overall survival. In contrast to current treatment strategies, patients did not have to undergo surgical stereotactic biopsy, which can sometimes lead to complications, to be included in this protocol.
MATERIALS AND METHODS: We retrospectively reviewed all the cases of DIPG that were treated in our department from September 15, 2004 to September 15, 2014. We compared the group of patients who followed our BSG 98 protocol to those who were treated with new targeted therapy protocols where systematic biopsy was required.
RESULTS: Patients in the BSG 98 protocol were treated with BCNU, cisplatin, and methotrexate, followed by radiation at disease progression. Targeted therapy protocols included radiation therapy along with treatment by erlotinib, cilengitide, or an association of nimotuzumab and vinblastine. Sixteen patients were treated with the BSG 98 protocol, and 9 patients were treated with new targeted therapy protocols. Median overall survival was significantly higher in the BSG 98 group compared to the targeted therapy group (16.1 months (95 % CI, 10.4-19.0) vs 8.8 months (95 % CI 1.4-12.3); p = 0.0003). An increase in the median progression-free survival was observed (respectively, 8.6 vs 3.0 months; p = 0.113).
CONCLUSION: The present study confirms that the BSG 98 protocol is one of the most effective current treatment strategies for DIPG. It may be used as the control arm in randomized trials investigating the use of innovative treatments and may be proposed to families who are averse to biopsy.

Related: Brain Stem Glioma - Childhood

Hu X, Fang Y, Hui X, et al.
Radiotherapy for diffuse brainstem glioma in children and young adults.
Cochrane Database Syst Rev. 2016; (6):CD010439 [PubMed] Related Publications

BACKGROUND: Diffuse brainstem glioma is a devastating disease with very poor prognosis. The most commonly used radiological treatment is conventional fractionated radiation. So far, there is no meta-analysis or systematic review available that assesses the benefits or harms of radiation in people with diffuse brainstem glioma.
OBJECTIVES: To assess the effects of conventional fractionated radiotherapy (with or without chemotherapy) versus other therapies (including different radiotherapy techniques) for newly diagnosed diffuse brainstem gliomas in children and young adults aged 0 to 21 years.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE/PubMed, and EMBASE to 19 August 2015. We scanned conference proceedings from the International Society for Paediatric Oncology (SIOP), International Symposium on Paediatric Neuro-Oncology (ISPNO), Society of Neuro-Oncology (SNO), and European Association of Neuro-Oncology (EANO) from 1 January 2010 to 19 August 2015. We searched trial registers including the International Standard Randomised Controlled Trial Number (ISRCTN) Register, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and the register of the National Institutes of Health to 19 August 2015. We imposed no language restrictions.
SELECTION CRITERIA: All randomised controlled trials (RCTs), quasi-randomised trials (QRCTs), or controlled clinical trials (CCTs) that compared conventional fractionated radiotherapy (with or without chemotherapy) versus other therapies (including different radiotherapy techniques) for newly diagnosed diffuse brainstem glioma in children and young adults aged 0 to 21 years.
DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies for inclusion, extracted data, assessed the risk of bias in each eligible trial, and conducted GRADE assessment of included studies. We resolved disagreements through discussion. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions.
MAIN RESULTS: We identified two RCTs that fulfilled our inclusion criteria. The two trials tested different comparisons.One multi-institutional RCT included 130 participants and compared hyperfractionated radiotherapy (six-week course with twice a day treatment of 117 cGy per fraction to a total dose of 7020 cGy) with conventional radiotherapy (six-week course with once a day treatment of 180 cGy per fraction to a total dose of 5400 cGy). The median time overall survival (OS) was 8.5 months in the conventional group and 8.0 months in the hyperfractionated group. We detected no clear evidence of effect on OS or event-free survival (EFS) in participants receiving hyperfractionated radiotherapy compared with conventional radiotherapy (OS: hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.75 to 1.53; EFS: HR 1.26, 95% CI 0.83 to 1.90). Radiological response (risk ratio (RR) 0.94, 95% CI 0.54 to 1.63) and various types of toxicities were similar in the two groups. There was no information on other outcomes. According to the GRADE approach, we judged the quality of evidence to be low (i.e. further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate) for OS and EFS, and very low (i.e. we are very uncertain about the estimate) for radiological response and toxicities.The second RCT included 71 participants and compared hypofractionated radiotherapy (39 Gy in 13 fractions over 2.6 weeks, 3 Gy per fraction) with conventional radiotherapy (54 Gy in 30 fractions over six weeks, 1.8 Gy per fraction). This trial reported a median OS of 7.8 months for the hypofractionated group and 9.5 months for the conventional group. It reported a progression-free survival (PFS) of 6.3 months for the hypofractionated group and 7.3 months for the conventional group. We found no clear evidence of effect on OS (HR 1.03, 95% CI 0.53 to 2.01) or PFS (HR 1.19, 95% CI 0.63 to 2.22) in participants receiving hypofractionated radiotherapy when compared with participants receiving conventional radiotherapy. The mainly observed adverse effect was local erythema and dry desquamation especially behind the auricles. There were some other toxicities, but there was no statistically significant difference between treatment groups. There was no information on other outcomes. We judged the quality of evidence to be moderate (i.e. further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate) for OS, and low for PFS and toxicities. It should be mentioned that the sample size in this RCT was small, which could lead to insufficient statistical power for a clinically relevant outcome.
AUTHORS' CONCLUSIONS: We could make no definitive conclusions from this review based on the currently available evidence. Further research is needed to establish the role of radiotherapy in the management of newly diagnosed diffuse brainstem glioma in children and young adults. Future RCTs should be conducted with adequate power and all relevant outcomes should be taken into consideration. Moreover, international multicentre collaboration is encouraged. Considering the potential advantage of hypofractionated radiotherapy to decrease the treatment burden and increase the quality of remaining life, we suggest that more attention should be paid to hypofractionated radiotherapy.

Related: Childhood Brain Tumours Childhood Brain Tumors Brain Stem Glioma - Childhood

Massimino M, Biassoni V, Gandola L, et al.
Childhood medulloblastoma.
Crit Rev Oncol Hematol. 2016; 105:35-51 [PubMed] Related Publications

Medulloblastoma accounts for 15-20% of childhood nervous system tumours. The risk of dying was reduced by 30% in the last twenty years. Patients are divided in risk strata according to post-surgical disease, dissemination, histology and some molecular features such as WNT subgroup and MYC status. Sixty to 70% of patients older than 3 years are assigned to the average-risk group. High-risk patients include those with disseminated and/or residual disease, large cell and/or anaplastic histotypes, MYC genes amplification. Current and currently planned clinical trials will: (1) evaluate the feasibility of reducing both the dose of craniospinal irradiation and the volume of the posterior fossa radiotherapy (RT) for those patients at low biologic risk, commonly identified as those having a medulloblastoma of the WNT subgroup; (2) determine whether intensification of chemotherapy (CT) or irradiation can improve outcome in patients with high-risk disease; (3) find target therapies allowing tailored therapies especially for relapsing patients and those with higher biological risk.

Related: Childhood Medulloblastoma / PNET Medulloblastoma

Malbari F, Gershon TR, Garvin JH, et al.
Psychiatric manifestations as initial presentation for pediatric CNS germ cell tumors, a case series.
Childs Nerv Syst. 2016; 32(8):1359-62 [PubMed] Article available free on PMC after 01/08/2017 Related Publications

BACKGROUND: Central nervous system (CNS) germ cell tumors account for 3 % of all pediatric brain tumors in the USA. Presenting symptoms are typically location based with pineal tumors presenting with obstructive hydrocephalus and suprasellar tumors with hypothalamic/pituitary dysfunction and ophthalmologic abnormalities. Psychiatric manifestations such as psychosis and behavioral changes are atypical presentations of CNS germ cell tumors, with only 11 previously reported cases.
METHODS: This is a retrospective case series describing patients with CNS germ cell tumors with an atypical presentation including psychiatric manifestations. Information regarding clinical presentation, treatment course, and outcome were obtained.
RESULTS: We report seven patients who presented with psychiatric symptoms consisting of psychomotor delay as well as behavioral and mood changes. Six of the seven patients were diagnosed ≥6 months after onset of psychiatric symptoms. All of the seven are alive but five continue to have neurologic and psychiatric issues post treatment.
CONCLUSIONS: Atypical presentations of CNS germ cell tumors can delay diagnosis and treatment and may be secondary to atypical locations as well as endocrine dysfunction manifesting as psychiatric symptoms. Delayed diagnosis did not appear to affect survival but earlier diagnosis may potentially be associated with better neurologic and psychiatric outcome. Patients who present with these symptoms and atypical neuroimaging should have a thorough evaluation for CNS germ cell tumors including serum and CSF markers. Clinicians should be aware of these less common presentations to aid in prompt diagnosis and treatment.

Related: Childhood Brain Tumours Childhood Brain Tumors Germ Cell Tumors Germ Cell Tumours in Children and Young Adults Germ Cell Tumors (Pediatric)

Emelifeonwu JA, Sokol D, Gallo P, et al.
Long-tunnelled external ventricular drain as a long-term treatment option for hydrocephalus in a child with an unresectable low-grade supratentorial tumor: case report.
J Neurosurg Pediatr. 2016; 18(4):430-433 [PubMed] Related Publications

The authors report a case of a child with hypothalamic-origin pilocytic astrocytoma and hydrocephalus, which was refractory to treatment with a ventriculoperitoneal shunt due to high CSF protein content. With parental education, the child's hydrocephalus was managed long-term in the community with a long-tunnelled external ventricular drain, which was maintained by his parents. To the authors' knowledge this is the first report of this management option as a long-term measure. No harm has come to the patient. The authors propose long-term, long-tunnelled external ventricular drain as a viable treatment option for such patients.

Robinson GW, Witt H, Resnick A
Exploiting Laboratory Insights to Improve Outcomes of Pediatric Central Nervous System Tumors.
Am Soc Clin Oncol Educ Book. 2016; 35:e540-6 [PubMed] Related Publications

Over a relatively short period of time, owing to improvements in biotechnology, our ability to identify the molecular mechanisms within pediatric brain tumors has dramatically increased. These findings have reshaped the way that we describe these diseases and have provided insights into how to better treat these often devastating diseases. Although still far from reaching the full therapeutic potential these advancements hold, the impact of these findings is steadily taking hold of pediatric brain tumor management. In this article, we summarize the major discoveries within three common pediatric brain tumor categories; medulloblastoma, ependymoma, and low-grade glioma. We discuss the current impact of these findings on treatment and the direction these findings may take the field of pediatric neuro-oncology.

Related: Childhood Brain Tumours Childhood Brain Tumors Brain and Spinal Cord Tumours Childhood Ependymoma Brain Stem Glioma - Childhood Childhood Medulloblastoma / PNET Medulloblastoma

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