Multi-parametric MR Imaging Biomarkers Associated to Clinical Outcomes in Gliomas: A Systematic Review

[EN] Purpose: To systematically review evidence regarding the association of multi-parametric biomarkers with clinical outcomes and their capacity to explain relevant subcompartments of gliomas. Materials and Methods: Scopus database was searched for original journal papers from January 1st, 2007 to February 20th , 2017 according to PRISMA. Four hundred forty-nine abstracts of papers were reviewed and scored independently by two out of six authors. Based on those papers we analyzed associations between biomarkers, subcompartments within the tumor lesion, and clinical outcomes. From all the articles analyzed, the twenty-seven papers with the highest scores were highlighted to represent the evidence about MR imaging biomarkers associated with clinical outcomes. Similarly, eighteen studies defining subcompartments within the tumor region were also highlighted to represent the evidence of MR imaging biomarkers. Their reports were critically appraised according to the QUADAS-2 criteria. Results: It has been demonstrated that multi-parametric biomarkers are prepared for surrogating diagnosis, grading, segmentation, overall survival, progression-free survival, recurrence, molecular profiling and response to treatment in gliomas. Quantifications and radiomics features obtained from morphological exams (T1, T2, FLAIR, T1c), PWI (including DSC and DCE), diffusion (DWI, DTI) and chemical shift imaging (CSI) are the preferred MR biomarkers associated to clinical outcomes. Subcompartments relative to the peritumoral region, invasion, infiltration, proliferation, mass effect and pseudo flush, relapse compartments, gross tumor volumes, and high-risk regions have been defined to characterize the heterogeneity. For the majority of pairwise cooccurrences, we found no evidence to assert that observed co-occurrences were significantly different from their expected co-occurrences (Binomial test with False Discovery Rate correction, alpha=0.05). The co-occurrence among terms in the studied papers was found to be driven by their individual prevalence and trends in the literature. Conclusion: Combinations of MR imaging biomarkers from morphological, PWI, DWI and CSI exams have demonstrated their capability to predict clinical outcomes in different management moments of gliomas. Whereas morphologic-derived compartments have been mostly studied during the last ten years, new multi-parametric MRI approaches have also been proposed to discover specific subcompartments of the tumors. MR biomarkers from those subcompartments show the local behavior within the heterogeneous tumor and may quantify the prognosis and response to treatment of gliomas.This work was supported by the Spanish Ministry for Investigation, Development and Innovation project with identification number DPI2016-80054-R.Oltra-Sastre, M.; Fuster García, E.; Juan -Albarracín, J.; Sáez Silvestre, C.; Perez-Girbes, A.; Sanz-Requena, R.; Revert-Ventura, A.... (2019). 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Presurgical neuropsychological and behavioral evaluation of children with posterior fossa tumors: Clinical article

Object. Brain tumors are associated with behavioral and neuropsychological effects. Most available data are focused on the posttreatment neurological and cognitive deficits of these patients. The aim of the present study was to investigate the pretreatment neuropsychological and behavioral impairment in children with posterior fossa tumors. Methods. The authors studied 24 children with posterior fossa tumors who were between 4 and 15 years of age, and who were surgically treated at the authors' institute. During the period prior to the tumor excision, neuropsychological and behavioral assessments were performed. A control group of age-matched children was also studied. The children's executive functions were assessed using the short form of the Wechsler Intelligence Scale for Children (WISC). For the assessment of visuospatial functions, spatial memory, and visuomotor integration skills, the Bender-Gestalt Test (BGT) was used. For assessment of the visual perception and visual memory, the authors used the Benton Visual Retention Test (BVRT). Furthermore, parents or caregivers completed the Child Behavior Checklist (CBCL). Results. The WISC revealed no significant difference between patients and the control group. The CBCL revealed significant somatic concerns compared with the measure's norms. Furthermore, the patients differed in aggressiveness, somatic concerns, anxiety symptoms, internalizing of problems, and total problems. In the BGT and the BVRT results, no significant difference was observed between patients and the control group. Furthermore, no significant correlation was found between neuropsychological scores and sex, age at diagnosis, histological diagnosis, presence of hydrocephalus, degree of hydrocephalus, tumor size, and tumor location. Conclusions. Children with posterior fossa tumors suffer more frequently from somatic concerns, aggressiveness, anxiety, and internalizing disorders compared with controls. No difference was found with respect to intelligence scores

Monoamine metabolites in ventricular CSF of children with posterior fossa tumors: Correlation with tumor histology and cognitive functioning. Clinical article

Object. The biogenic amines (dopamine, epinephrine, norepinephrine, and serotonin) are involved in the regulation of multiple neuronal functions, and changes in monoamine concentrations in the CSF have been detected in several disorders. The aim of the present study was to investigate the role of biogenic amines in the ventricular CSF of children suffering from posterior fossa tumors and their possible correlation with tumor histology and cognitive functioning. Methods. Twenty-two children with posterior fossa tumors who were treated surgically at Children's Hospital "Agia Sofia" were studied. Patients ranged in age from 5.5 to 15 years. The study population included patients who suffered from hydrocephalus and were treated by ventriculoperitoneal shunt placement. During the operation for shunt placement, a CSF sample was obtained for the assessment of 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA). Simultaneously, a blood sample was also obtained for assessment of the same metabolites in the serum. The concentration of vanillylmandelic acid (VMA) was evaluated in 24-hour urine samples in 11 patients. Cerebrospinal fluid from a control group of children was also studied. Executive functions were assessed using the short form of the Wechsler Intelligence Scale for Children (WISC). Results. Twelve patients suffered from astrocytomas, 9 from medulloblastomas, and 1 from an ependymoma. The MHPG concentration in CSF was significantly higher in patients with astrocytomas compared with patients with medulloblastomas. Twenty-four-hour urine samples of VMA were significantly higher in patients with astrocytomas compared with patients with medulloblastomas. The MHPG concentration in CSF was negatively correlated with the verbal scale of the WISC and there was a trend toward a significant negative correlation with the total WISC score. Homovanillic acid in CSF was positively correlated with the performance scale of the WISC. There was a significant correlation between HVA and MHPG levels in CSF. The CSF concentration of 5-HIAA was significantly correlated with the HVA concentration in serum. Twenty-four-hour urine VMA samples were statistically significantly correlated with HVA concentration in both CSF and serum, with MHPG in CSF, and with 5-HIAA in serum. Conclusions. This study showed that children with posterior fossa tumors have differences in the levels of monoamine metabolites in CSF. Further studies with a larger number of patients are obviously needed to verify these observations as well as studies to correlate the monoamine metabolite levels with the neuropsychological and behavioral findings in children with posterior fossa tumors. ©AANS, 2014

Intramedullary spinal cord primitive neuroectodermal tumor presenting with hydrocephalus

Spinal primitive neuroectodermal tumors are exceedingly rare. Herewith, we present the first case of an intramedullary spinal cord tumor associated with hydrocephalus in a 2-month-old boy that presented with left hemiparesis. The patient had been diagnosed on prenatal ultrasound with enlarged ventricular system. At his current admission, a brain magnetic resonance imaging (MRI) revealed hydrocephalus and an intramedullary lesion extending from the second cervical to the first thoracic vertebrae. Dissemination of the tumor was revealed intracranially and in the spinal canal. After a ventriculoperitoneal shunt placement a radical resection of the tumor was performed, however some small tumor remnants could not be safely removed. Postoperative there was no neurologic deterioration. The tumor was diagnosed as a central nervous system primitive neuroectodermal tumor (World Health Organization grade IV). Spinal intramedullary primitive neuroectodermal tumors are extremely rare. In such rare tumors, multiinstitutional studies are needed for treatment guidelines to be established. © The Author(s) 2013