Trends in reported incidence of primary malignant brain tumors in children in the United States.
BACKGROUND The reported incidence of primary malignant brain tumors among children in the United States increased by 35% during the period from 1973 through 1994. The purpose of our study was twofold: 1) to determine whether the reported incidence rates for this period are better represented by a linear increase over the entire period ("linear model") or, alternatively, by a step function, with a lower rate in the years preceding 1984-1985 and a constant higher rate afterward ("jump model"); and 2) to identify the specific brain regions and histologic subtypes that have increased in incidence. METHODS Incidence data from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute for the period from 1973 through 1994 for primary malignant brain tumors in children were used to model the number of cases in a year as a random variable from a Poisson distribution by use of either a linear model or a jump model. RESULTS/CONCLUSIONS The increase in reported incidence of childhood primary malignant brain tumors is best explained by the jump model, with a step increase in incidence occurring in the mid-1980s. The brain stem and the cerebrum are the primary sites for which an increase in tumor incidence has been reported. The increase in reported incidence of low-grade gliomas in the cerebrum and the brain stem (unaccompanied by an increase in mortality for these sites) supports the substantial contribution of low-grade gliomas to the overall increase in reported incidence for childhood brain tumors. IMPLICATIONS The significantly better fit of the data to a jump model supports the hypothesis that the observed increase in incidence somehow resulted from changes in detection and/or reporting of childhood primary malignant brain tumors during the mid-1980s.
Disrupting the CD47-SIRPα anti-phagocytic axis by a humanized anti-CD47 antibody is an efficacious treatment for malignant pediatric brain tumors
Anti-CD47 antibody is effective for treating malignant pediatric brain tumors without detectable toxicity in patient-derived xenograft models. Brain tumors, meet macrophages A protein called CD47 is often expressed on the surface of tumor cells, where it serves as a “don’t eat me” signal that blocks macrophages from attacking the tumor. To overcome this signal and allow the macrophages to “eat” tumor cells, Gholamin et al. engineered a humanized antibody that blocks CD47 signaling. The researchers tested the efficacy of this antibody in patient-derived xenograft models of a variety of pediatric brain tumors. The treatment was successful at inhibiting CD47, killing tumor cells, and prolonging the animals’ survival, all without toxic effects on normal tissues. Morbidity and mortality associated with pediatric malignant primary brain tumors remain high in the absence of effective therapies. Macrophage-mediated phagocytosis of tumor cells via blockade of the anti-phagocytic CD47-SIRPα interaction using anti-CD47 antibodies has shown promise in preclinical xenografts of various human malignancies. We demonstrate the effect of a humanized anti-CD47 antibody, Hu5F9-G4, on five aggressive and etiologically distinct pediatric brain tumors: group 3 medulloblastoma (primary and metastatic), atypical teratoid rhabdoid tumor, primitive neuroectodermal tumor, pediatric glioblastoma, and diffuse intrinsic pontine glioma. Hu5F9-G4 demonstrated therapeutic efficacy in vitro and in vivo in patient-derived orthotopic xenograft models. Intraventricular administration of Hu5F9-G4 further enhanced its activity against disseminated medulloblastoma leptomeningeal disease. Notably, Hu5F9-G4 showed minimal activity against normal human neural cells in vitro and in vivo, a phenomenon reiterated in an immunocompetent allograft glioma model. Thus, Hu5F9-G4 is a potentially safe and effective therapeutic agent for managing multiple pediatric central nervous system malignancies.
neural network support vector machine deep learning convolutional neural network convolutional neural image segmentation magnetic resonance magnetic resonance imaging division multiple acces resonance imaging confidence interval rayleigh fading channel division multiple bayesian model conditional random field human brain brain tumor block code magnetic resonance image classification problem turbo code mri image decoding algorithm nervous system convolutional code stem cell automatic segmentation analysis and application space-time block positron emission tomography white matter space-time block code transmit antenna emission tomography biometric authentication cellular phone positron emission tumor segmentation central nervous system time division multiple graph partitioning brain tumor segmentation bch code space-time code space-time block coding tumor detection piston pump tumor growth central nervou linear block code partitioning algorithm tumor cell linear block orthogonal space-time block biometric authentication system brain tumor detection sensor location brain magnetic resonance axial piston growth factor diagnostic accuracy axial piston pump orthogonal space-time tumor classification national cancer emergent behavior current concept bayesian modelling rat brain brain tumor classification brain tumor image quasi-orthogonal space-time block graph partitioning algorithm tumor image automatic brain tumor glioblastoma multiforme neural stem cell number of transmit emergent technology contrast media multimodal brain tumor tumor segmentation method neural stem tumor image segmentation tumor type brain tumor patient malignant brain tumor brain tumor type primary brain tumor human brain tumor pediatric brain malignant brain tumor imaging brain tumor growth brain tumor surgery primary brain tumor surgery k-way partitioning primary malignant neoplasm of brain anaplastic astrocytoma cns disorder non-small cell lung carcinoma protein tyrosine kinase adverse reaction to drug recurrent childhood brain stem glioma brain neoplasm childhood brain stem glioma neoplasms, intracranial pituitary neoplasm millimole per kilogram angiogenic proces xenograft procedure small cell carcinoma of lung gadopentetate dimeglumine hematology (discipline) high-grade childhood cerebral astrocytoma childhood brain tumor united state