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Diagnostics (Basel, Switzerland) Apr 2022Primary brain tumors are the most common solid neoplasms in children and a leading cause of mortality in this population. MRI plays a central role in the diagnosis,... (Review)
Review
Primary brain tumors are the most common solid neoplasms in children and a leading cause of mortality in this population. MRI plays a central role in the diagnosis, characterization, treatment planning, and disease surveillance of intracranial tumors. The purpose of this review is to provide an overview of imaging methodology, including conventional and advanced MRI techniques, and illustrate the MRI appearances of common pediatric brain tumors.
PubMed: 35454009
DOI: 10.3390/diagnostics12040961 -
BMC Cancer Dec 2022Juvenile Pilocytic Astrocytomas (JPAs) are one of the most common pediatric brain tumors, and they are driven by aberrant activation of the mitogen-activated protein...
BACKGROUND
Juvenile Pilocytic Astrocytomas (JPAs) are one of the most common pediatric brain tumors, and they are driven by aberrant activation of the mitogen-activated protein kinase (MAPK) signaling pathway. RAF-fusions are the most common genetic alterations identified in JPAs, with the prototypical KIAA1549-BRAF fusion leading to loss of BRAF's auto-inhibitory domain and subsequent constitutive kinase activation. JPAs are highly vascular and show pervasive immune infiltration, which can lead to low tumor cell purity in clinical samples. This can result in gene fusions that are difficult to detect with conventional omics approaches including RNA-Seq.
METHODS
To this effect, we applied RNA-Seq as well as linked-read whole-genome sequencing and in situ Hi-C as new approaches to detect and characterize low-frequency gene fusions at the genomic, transcriptomic and spatial level.
RESULTS
Integration of these datasets allowed the identification and detailed characterization of two novel BRAF fusion partners, PTPRZ1 and TOP2B, in addition to the canonical fusion with partner KIAA1549. Additionally, our Hi-C datasets enabled investigations of 3D genome architecture in JPAs which showed a high level of correlation in 3D compartment annotations between JPAs compared to other pediatric tumors, and high similarity to normal adult astrocytes. We detected interactions between BRAF and its fusion partners exclusively in tumor samples containing BRAF fusions.
CONCLUSIONS
We demonstrate the power of integrating multi-omic datasets to identify low frequency fusions and characterize the JPA genome at high resolution. We suggest that linked-reads and Hi-C could be used in clinic for the detection and characterization of JPAs.
Topics: Child; Adult; Humans; Multiomics; Proto-Oncogene Proteins B-raf; Oncogene Proteins, Fusion; Astrocytoma; Brain Neoplasms; Receptor-Like Protein Tyrosine Phosphatases, Class 5
PubMed: 36503484
DOI: 10.1186/s12885-022-10359-z -
La Clinica Terapeutica 2022Histograms can be determined throughout tumors, relying partly on existing tumor microstructure knowledge and the sampling effect from area of interest analyses. We...
PURPOSE
Histograms can be determined throughout tumors, relying partly on existing tumor microstructure knowledge and the sampling effect from area of interest analyses. We aimed to investigate the impact of ADC histogram parameters in discriminating medulloblastoma, ependymoma, and pilocytic astrocytoma.
METHODS
This study received approval from the Institutional Ethics Review Committee of Children's Hospital 02. Processes were conducted according to relevant laws and regulations, and requirements for written informed consent were fulfilled. The study involved 24 patients at Children's Hospital 02 from February-December 2019. Group 1 included 12 children with medulloblastoma, group 2 included 5 with ependymoma, and group 3 included 7 with pilocytic astrocytoma. All patients underwent MRI followed by surgery or biopsy to obtain histopathological confirmations.
RESULTS
Our analysis indicated that AUC, sensitivity, and specificity were 96.7%, 91.7%, and 100%, respectively when ADCkurtosis (cut-off point = 2.34) was taken to differentiate between medulloblasto-mas and ependymomas. To distinguish between medulloblastomas and pilocytic astrocytomas, the cut-off points of ADCmean, ADCmedian, ADCmax, ADCmin, rADCmean, rADCmax, and rADCmin of 0.985, 0.910, 1.305, 0.710, 1.349, 1.738, and 1.251, were taken respectively with AUC, sensitivity, and specificity elicited at 100%. To discriminate between ependymomas and pilocytic astrocytomas, the cut-off points of ADCmean, ADCmedian, ADCmax, ADCmin, rADCmean, rADC-median, rADCmax and rADCmin were 1.010, 0.930, 1.270, 0.735, 1.346, 1.324, 1.676, and 1.273, respectively, with AUC, sensitivity, and specificity at 100%.
CONCLUSION
ADC histograms can facilitate differentiation among juvenile medulloblastoma, ependymoma, and pilocytic astrocytoma, providing reliable, objective evidence of tumor differentiation.
Topics: Astrocytoma; Cerebellar Neoplasms; Child; Diffusion Magnetic Resonance Imaging; Ependymoma; Humans; Medulloblastoma; Retrospective Studies
PubMed: 35857056
DOI: 10.7417/CT.2022.2448 -
Pathologica Dec 2022The WHO 2021 classification of central nervous system cancers distinguishes diffuse gliomas that arise in adults (referred to as the "adult type") and those that arise... (Review)
Review
The WHO 2021 classification of central nervous system cancers distinguishes diffuse gliomas that arise in adults (referred to as the "adult type") and those that arise in children (defined as "paediatric") based on clinical and molecular characteristics."). However, paediatric-type gliomas may occasionally be present in younger adults and occasionally adult-type gliomas may occur in children. Diffuse low-grade paediatric glioma includes diffuse astrocytoma altered by MYB or MYBL1, low-grade polymorphic juvenile neuroepithelial tumour, angiocentric glioma, and diffuse low-grade glioma with an altered MAPK pathway. Here, we examine these newly recognised entities according to WHO diagnostic criteria and propose an integrated diagnostic approach that can be used to separate these clinically and biologically distinct tumor groups.
Topics: Adult; Child; Humans; Brain Neoplasms; Glioma
PubMed: 36534420
DOI: 10.32074/1591-951X-828 -
AJNR. American Journal of Neuroradiology Mar 1998We report the common characteristics of juvenile pilocytic astrocytomas revealed by proton MR spectroscopy. (Review)
Review
PURPOSE
We report the common characteristics of juvenile pilocytic astrocytomas revealed by proton MR spectroscopy.
METHODS
Eight children with pilocytic astrocytomas were studied with proton MR spectroscopy. The selected sampling volume was approximately 4 cm3, obtained from solid tumor. To localize the sampling volume, we used point-resolved spectroscopy (PRESS) and stimulated-echo acquisition mode (STEAM) techniques to acquire long- and short-TE spectra, respectively. Spectra from PRESS and STEAM sequences were processed using Lorentzian-to-Gaussian transformation and exponential apodization, respectively. For PRESS (2000/270) spectra, peaks of creatine, choline, N-acetylaspartate (NAA), and lactate resonances were integrated; for STEAM (2000/20) spectra, we measured the amplitude of the peaks at 3.2, 2.0, 1.3 and 0.9 ppm.
RESULTS
An elevated lactate doublet was observed in the PRESS spectra. The choline/NAA ratio was 3.40. The amplitude ratios of the lipid pattern (0.9, 1.3 and 2.0 ppm) to choline were all below one.
CONCLUSION
Despite the benign histology of the tumor, which generally lacks necrosis, a lactate signal was detected in all eight patients studied. A dominant lipid pattern was not observed.
Topics: Aspartic Acid; Astrocytoma; Brain Neoplasms; Child; Child, Preschool; Choline; Humans; Infant; Lactic Acid; Lipid Metabolism; Magnetic Resonance Spectroscopy; Protons
PubMed: 9541314
DOI: No ID Found -
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 -
Cancers Dec 2023Congenital tumors are rare and, owing to this rarity, there is limited information on many of them. A total of 839 fetal and postnatal MRI studies performed in the first...
Congenital tumors are rare and, owing to this rarity, there is limited information on many of them. A total of 839 fetal and postnatal MRI studies performed in the first 3 months of life were retrospectively reviewed. They were performed with the use of 1.5 T scanners. Seventy-six tumors were diagnosed based on fetal MRI between 20 and 37 gestational weeks, and 27 were found after birth, from 1 day of age to 3 months of life. Teratomas were the most common tumors in our dataset, mainly in the sacrococcygeal region (SCT), followed by cardiac rhabdomyomas and subependymal giant cell astrocytomas (SEGA) associated with TSC, and neuroblastomas. The group of less common tumors consisted of infantile fibrosarcomas, malignant rhabdoid tumors, mesoblastic nephromas and Wilms tumor, craniopharyngiomas, brain stem gliomas, desmoplastic infantile astrocytoma, choroid plexus carcinoma, glioblastoma, hemangiopericytoma, rhabdomyosarcoma, melanoma, mesenchymal hamartomas of the chest wall and the liver, and juvenile xanthogranuloma, with special consideration of blue rubber bleb nevus syndrome. MRI plays a significant role in further and better characterization of congenital tumors, leading to a correct diagnosis in many cases, which is crucial for pregnancy and neonatal management and psychological preparation of the parents. No diagnosis is impossible and can be absolutely excluded.
PubMed: 38201471
DOI: 10.3390/cancers16010043 -
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 -
Translational Oncology Jun 2022Brain tumors are the leading cause of cancer-related deaths in children. Tailored therapies need preclinical brain tumor models representing a wide range of molecular...
Brain tumors are the leading cause of cancer-related deaths in children. Tailored therapies need preclinical brain tumor models representing a wide range of molecular subtypes. Here, we adapted a previously established brain tissue-model to fresh patient tumor cells with the goal of establishing3D in vitro culture conditions for each tumor type.Wereported our findings from 11 pediatric tumor cases, consisting of three medulloblastoma (MB) patients, three ependymoma (EPN) patients, one glioblastoma (GBM) patient, and four juvenile pilocytic astrocytoma (Ast) patients. Chemically defined media consisting of a mixture of pro-neural and pro-endothelial cell culture medium was found to support better growth than serum-containing medium for all the tumor cases we tested. 3D scaffold alone was found to support cell heterogeneity and tumor type-dependent spheroid-forming ability; both properties were lost in 2D or gel-only control cultures. Limited in vitro models showed that the number of differentially expressed genes between in vitro vs. primary tissues, are 104 (0.6%) of medulloblastoma, 3,392 (20.2%) of ependymoma, and 576 (3.4%) of astrocytoma, out of total 16,795 protein-coding genes and lincRNAs. Two models derived from a same medulloblastoma patient clustered together with the patient-matched primary tumor tissue; both models were 3D scaffold-only in Neurobasal and EGM 1:1 (v/v) mixture and differed by a 1-mo gap in culture (i.e., 6wk versus 10wk). The genes underlying the in vitrovs. in vivo tissue differences may provide mechanistic insights into the tumor microenvironment. This study is the first step towards establishing a pipeline from patient cells to models to personalized drug testing for brain cancer.
PubMed: 35381525
DOI: 10.1016/j.tranon.2022.101407