Delayed Fluorodeoxyglucose Positron Emission Tomography Imaging in the Differentiation of Tumor Recurrence and Radiation Necrosis in Pediatric Central Nervous System Tumors: Case Report and Review of the Literature.

Malignant central nervous system (CNS) tumors are often treated with radiation therapy, after which clinical and radiographic sequelae can lead to difficulties differentiating tumor recurrence from treatment effect. Magnetic resonance imaging (MRI) is often unable to distinguish between these two entities. The improved ability to delineate concerning foci could lead to earlier tumor detection with quicker access to new therapies and/or clinical trials; conversely, it could alleviate patient concerns in the case of radiation necrosis as the etiology. The utility of positron emission tomography with computed tomography (PET/CT) imaging with fluorodeoxyglucose (FDG) has been explored in CNS tumors in the past, as this imaging modality is widely used in oncologic practices. As there are concerns with false positive imaging in the case of cells with a high metabolic uptake due to causes other than malignancy (i.e. infection, inflammation), delayed FDG PET imaging has been proposed as a mechanism to reduce this confusion. Delayed FDG PET imaging has been explored in several adult and pediatric malignancies, including adult CNS tumors, though there are no current publications applying its use in pediatric CNS tumors. We present two cases of pediatric CNS tumors, where delayed FDG PET imaging helped in the early diagnosis of a recurrence through a distinguishing tumor from the treatment effect.

Bromodomain Inhibitor Review: Bromodomain and Extra-terminal Family Protein Inhibitors as a Potential New Therapy in Central Nervous System Tumors.

The bromodomain and extraterminal (BET) family proteins associate with transcriptional activation through interaction with acetylated chromatin, therefore playing a key role as epigenetic regulators. BET proteins serve to regulate the expression of importance oncogenes, including those involved in apoptosis as well as cell cycle progression. Due to this potential as an epigenetic target, small molecule inhibition of BET proteins have been investigated and demonstrate promising activity in both solid and hematologic malignancies, including brain tumors. Glioblastoma multiforme (GBM), subsets of medulloblastoma, and diffuse intrinsic pontine glioma (DIPG) are types of brain tumors with dismal prognoses, and as such have been the subjects of preclinical studies using BET inhibitors both in vivo and in vitro. While results from these preclinical investigations have shown promise, clinical trials are in early phases at this time. In this review, we will summarize the current literature on BET family proteins, their potential as therapeutic targets in brain tumors as well as other malignancies, and the preclinical and clinical investigations that have been undertaken to date.

Gastroschisis and maternal intake of phytoestrogens.

The prevalence of gastroschisis has increased significantly in the past few decades. The strongest risks have been observed for women <25 years old or of low body mass index, and maternal diet also been proposed to be associated with risk. The objective of this study was to evaluate whether the risk of gastroschisis is associated with maternal dietary intake of phytoestrogens. The analysis includes data on mothers of 409 gastroschisis cases and 3,007 controls who delivered their infants from 2005 to 2010 and participated in the National Birth Defects Prevention Study, a multistate, population-based, case-control study. Detailed information was obtained from maternal telephone interviews that included a validated food frequency questionnaire. We conducted logistic regression analyses that included each phytoestrogen in its continuous form (to test for linearity) and quadratic form (to test for non-linearity), adjusted for maternal energy intake, age, BMI, race-ethnicity, and smoking in 1st trimester. Logistic regression analysis indicated that biochanin A, formonoetin, and coumestrol had a significant non-linear association with gastroschisis (P-value <0.05 for quadratic term). Lower intakes were associated with increased risk, with somewhat stronger but relatively modest associations at the lower end of the distribution; for example, the ORs for the 10th versus 50th percentiles ranged from 1.1 to 1.2. Associations were not significant for the other phytoestrogens. This study provides some evidence for association with certain phytoestrogens, after adjusting for covariates. The implications of our findings for clinical practice are uncertain pending other studies examining this association. © 2016 Wiley Periodicals, Inc.

Medulloblastoma Genotype Dictates Blood Brain Barrier Phenotype.

The childhood brain tumor, medulloblastoma, includes four subtypes with very different prognoses. Here, we show that paracrine signals driven by mutant ß-catenin in WNT-medulloblastoma, an essentially curable form of the disease, induce an aberrant fenestrated vasculature that permits the accumulation of high levels of intra-tumoral chemotherapy and a robust therapeutic response. In contrast, SHH-medulloblastoma, a less curable disease subtype, contains an intact blood brain barrier, rendering this tumor impermeable and resistant to chemotherapy. The medulloblastoma-endothelial cell paracrine axis can be manipulated in vivo, altering chemotherapy permeability and clinical response. Thus, medulloblastoma genotype dictates tumor vessel phenotype, explaining in part the disparate prognoses among medulloblastoma subtypes and suggesting an approach to enhance the chemoresponsiveness of other brain tumors.