Medulloblastoma is the most common malignant brain tumors in children. Current management combines surgery, radiotherapy, and chemotherapy. Current treatment of medulloblastoma is based on a clinical ...risk-stratification system that takes into account age, extent of resection and metastatic status. High-risk medulloblastoma patients are defined by the presence of metastatic disease and/or an incomplete resection with a residual amount of tumour>1.5 cm2. This review describes the evolution in the management of high-risk medulloblastoma patients during recent 4 decades and recent changes in the definition of high-risk patients as a result of major advances in the understanding of the molecular heterogeneity of medulloblastomas.
Recently identified molecular subgroups of medulloblastoma have shown potential for improved risk stratification. We hypothesized that distinct MR imaging features can predict these subgroups.
All ...patients with a diagnosis of medulloblastoma at one institution, with both pretherapy MR imaging and surgical tissue, served as the discovery cohort (n = 47). MR imaging features were assessed by 3 blinded neuroradiologists. NanoString-based assay of tumor tissues was conducted to classify the tumors into the 4 established molecular subgroups (wingless, sonic hedgehog, group 3, and group 4). A second pediatric medulloblastoma cohort (n = 52) from an independent institution was used for validation of the MR imaging features predictive of the molecular subtypes.
Logistic regression analysis within the discovery cohort revealed tumor location (P < .001) and enhancement pattern (P = .001) to be significant predictors of medulloblastoma subgroups. Stereospecific computational analyses confirmed that group 3 and 4 tumors predominated within the midline fourth ventricle (100%, P = .007), wingless tumors were localized to the cerebellar peduncle/cerebellopontine angle cistern with a positive predictive value of 100% (95% CI, 30%-100%), and sonic hedgehog tumors arose in the cerebellar hemispheres with a positive predictive value of 100% (95% CI, 59%-100%). Midline group 4 tumors presented with minimal/no enhancement with a positive predictive value of 91% (95% CI, 59%-98%). When we used the MR imaging feature-based regression model, 66% of medulloblastomas were correctly predicted in the discovery cohort, and 65%, in the validation cohort.
Tumor location and enhancement pattern were predictive of molecular subgroups of pediatric medulloblastoma and may potentially serve as a surrogate for genomic testing.
(
) status has important implications for prognosis and therapy of pediatric low-grade gliomas. Currently,
status classification relies on biopsy. Our aim was to train and validate a radiomics ...approach to predict
fusion and
V600E mutation.
In this bi-institutional retrospective study, FLAIR MR imaging datasets of 115 pediatric patients with low-grade gliomas from 2 children's hospitals acquired between January 2009 and January 2016 were included and analyzed. Radiomics features were extracted from tumor segmentations, and the predictive model was tested using independent training and testing datasets, with all available tumor types. The model was selected on the basis of a grid search on the number of trees, opting for the best split for a random forest. We used the area under the receiver operating characteristic curve to evaluate model performance.
The training cohort consisted of 94 pediatric patients with low-grade gliomas (mean age, 9.4 years; 45 boys), and the external validation cohort comprised 21 pediatric patients with low-grade gliomas (mean age, 8.37 years; 12 boys). A 4-fold cross-validation scheme predicted
status with an area under the curve of 0.75 (SD, 0.12) (95% confidence interval, 0.62-0.89) on the internal validation cohort. By means of the optimal hyperparameters determined by 4-fold cross-validation, the area under the curve for the external validation was 0.85. Age and tumor location were significant predictors of
status (
values = .04 and <.001, respectively). Sex was not a significant predictor (
value = .96).
Radiomics-based prediction of
status in pediatric low-grade gliomas appears feasible in this bi-institutional exploratory study.
Abstract Background Atypical teratoid rhabdoid tumours (ATRT) are aggressive brain tumours mostly occurring in early childhood. Largest published series arise from registries and institutional ...experiences (1–4). The aim of this report is to provide population-based data to further characterise this rare entity and to delineate prognostic factors. Patients and methods A national retrospective study of children ⩽18 years diagnosed with a central nervous system (CNS) ATRT between 1995 and 2007 was undertaken. All cases underwent central pathology review. Results There were 50 patients (31 males; median age at diagnosis of 16.7 months). Twelve patients were >36 months. Infratentorial location accounted for 52% of all cases. Nineteen patients (38%) had metastatic disease. Fifteen (30%) underwent gross total resection (GTR). Ten patients (20%) underwent palliation. Among the 40 remaining patients, 22 received conventional chemotherapy and 18 received high dose chemotherapy regimens (HDC); nine received intrathecal chemotherapy and 15 received adjuvant radiation. Thirty of the 40 treated patients relapsed/progressed at a median time of 5.5 months (0–32). The median survival time of the entire cohort was 13.5 months (1–117.5 months). Age, tumour location and metastatic status were not prognostic. Patients with GTR had a better survival (2 years overall survival (OS): 60% ± 12.6 versus 21.7% ± 8.5, p = 0.03). HDC conferred better outcome (2 years OS 47.9% ± 12.1 versus 27.3% ± 9.5, p = 0.036). Upfront radiation did not provide survival benefit. Six of the 12 survivors (50%) did not receive radiation. Conclusion The outcome of CNS ATRT remains poor. However, the use of HDC provides encouraging results. GTR is a significant prognostic factor. The role of adjuvant radiation remains unclear.
Although neoplasms of the brain and central nervous system (CNS) are relatively uncommon, comprising only 1–2% of the overall cancer burden, they represent a substantial source of morbidity and ...mortality worldwide. The age-adjusted annual incidence of CNS tumours is reportedly low; however, there is substantial global variability in its incidence, with nearly a five-fold difference between regions with the highest rates in developed countries in the West and those with the lowest rates in developing countries in South-East Asia, including India, possibly attributable to key differences in environmental factors, genetic susceptibilities and cultural practices, as well as resource constraints in low–middle income countries precluding precise ascertainment and accurate diagnosis. The burden of CNS tumours is further compounded by the fact that they require highly specialised and skilled multidisciplinary care, including access to modern neuroimaging, neurosurgery, neuropathology and molecular biology, radiotherapy, chemotherapy and rehabilitation services, which may not be widely available in an integrated manner in large parts of the world with a large variation in clinical pathways, non-uniformity of care and resultant heterogeneity in clinical outcomes. CNS tumours encompass a heterogeneous spectrum of histopathological entities with differences in presentation, distinct molecular/genetic alterations, diverse biological behaviour and varying clinical outcomes. Survival is highly dependent on histology, grade and molecular biology, but varies widely across continents, even for the same tumour type and grade. In general, survival is higher in children with primary brain tumours than in adults, largely due to the differences in histological distribution across age groups. However, there is widespread variability, with 5-year survival for paediatric brain tumours being <40% in some low–middle income countries compared with 70–80% in the developed world. This review compares the descriptive epidemiology and clinical outcomes of primary brain tumours between the East and the West that pose unique challenges but also provide new opportunities in contemporary neuro-oncological practice.
Cerebellar mutism syndrome (CMS) is an important medical challenge in the management of pediatric posterior fossa brain tumors, because it occurs in a subset of children following tumor resection. A ...definitive clinical profile and neuroanatomical substrate associated with CMS remains unclear. We investigated the relationship between presurgical and clinical variables and the incidence of CMS, along with diffusion tensor imaging, to characterize the integrity of cerebello-thalamo-cerebral white matter pathways. Seventeen children with posterior fossa tumors and CMS, 34 children with posterior fossa tumors without CMS, and 28 healthy children were enrolled in this study. Bilateral cerebello-thalamo-cerebral pathways were delineated and segmented into anatomical regions. Mean integrity measures for each region were compared among children with CMS, children without CMS, and healthy children. Left-handedness, medulloblastoma histology, and larger tumor size distinguished between patients with CMS and patients without CMS (P < .04). Right cerebellar white matter within the cerebello-thalamo-cerebral pathway was compromised in children with CMS relative to children without CMS and healthy children (P < .02). We provide a potential schema for CMS risk among children treated for posterior fossa tumors. Left-handed children treated for medulloblastoma may be the most at risk for CMS, and unilateral, localized damage within the cerebello-thalamo-cerebral pathway at the level of the right cerebellum is implicated in the presentation of CMS. This disruption in communication between the right cerebellum and left frontal cortex may contribute to speech-language problems observed in children with CMS. Our findings may be relevant for surgical planning and speech-language therapy to mitigate symptoms of CMS.
Abstract Aims We examined the efficacy of exercise training for improving physical functioning and cardiopulmonary fitness in survivors of paediatric brain tumours (BTs) treated with cranial ...irradiation. Methods We conducted a controlled clinical trial with crossover of exercise training versus no training in the community in either a group or combined group/home setting. A volunteer sample of 28 children treated with cranial irradiation for brain tumours completed training (mean age = 11.53 years; mean time since diagnosis = 5.25 years). end-points were physical functioning assessed by four subtests from the Bruininks–Oseretsky Test of motor performance (BOT-2) and pro-rated work rate from a cycle ergometer. Linear mixed modelling was used to evaluate time, training, training setting, and carryover effects. Results Adherence to training was 84%. Performance on the BOT-2 was below average for all assessments. However, training resulted in improvement in bilateral coordination (F (1, 30) = 6.59, p = 0.02), irrespective of training setting and improved performance was maintained even approximately 12°weeks after training had ended (F (1, 24) = 9.60, p = 0.005). Training resulted in increased pro-rated work rate for participants in the group training setting only (F (1, 25) = 4.57, p = 0.04) and these participants maintained their improved work rate approximately 12°weeks after training had ended (F (1, 20) = 8.38, p = 0.01). Conclusion Exercise training improves physical functioning and fitness in paediatric BT survivors. Exercise interventions that ameliorate adverse physical effects and promote health in long-term survivors are highly recommended in this vulnerable population. ( ClinicalTrials.gov , NCT01944761 ).
High-dose chemotherapy (HDC) strategies were developed in brain tumor protocols for young children to prevent neuropsychological (NP) impairments associated with radiotherapy. However, comprehensive ...NP evaluations of these children treated with such strategies remain limited. We examined the long-term neurocognitive outcomes of young children (<6 years) with medulloblastoma, treated similarly, with a HDC strategy “according to” the chemotherapy regimen of the protocol CCG 99703. This retrospective study included young children less than 6 years of age at diagnosis of medulloblastoma treated from 1998 to 2011 at 7 North American institutions. Twenty-four patients who had at least one NP assessment post-treatment are the focus of the current study. Of 24 patients in this review, 15 (63%) were male and the mean age at diagnosis was 29.4 months (SD = 13.5). Posterior fossa syndrome (PFs) was reported in five patients (21%). Nine (37.5%) received radiotherapy (5 focal, 4 craniospinal). On average, children were assessed 3.5 years (SD = 1.8) post-diagnosis, and full-scale intellectual quotient (FSIQ) scores ranged from 56 to 119 (
X
¯
= 92; SD = 16.8). The majority of children (74%) had low-average to average NP functioning. Very young children treated with radiotherapy, who needed hearing support or with PFs had worse neurocognitive outcomes. Clinically significant deficits (<10th percentile) in at least one area of NP functioning were found in 25% of the children. NP data obtained from this sample of survivors of medulloblastoma in early childhood, all treated with sequential HDC and 1/3 with radiotherapy, describe NP functioning within average normal limits overall. However, almost 25% of children had significant deficits in specific domains.
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