Faculty Bibliography
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284
Utility of MRI versus tumor markers for post-treatment surveillance of marker-positive CNS germ cell tumors
Patients with marker-positive central nervous system (CNS) germ cell tumors are typically monitored for tumor recurrence with both tumor markers (AFP and b-hCG) and MRI. We hypothesize that the recurrence of these tumors will always be accompanied by an elevation in tumor markers, and that surveillance MRI may not be necessary. We retrospectively identified 28 patients with CNS germ cell tumors treated at our institution that presented with an elevated serum or cerebrospinal fluid (CSF) tumor marker at the time of diagnosis. We then identified those who had a tumor recurrence after having been in remission and whether each recurrence was detected via MRI changes, elevated tumor markers, or both. Four patients suffered a tumor recurrence. Only one patient had simultaneously elevated tumor markers and MRI evidence of recurrence. Two patients had evidence of recurrence on MRI without corresponding elevations in serum or CSF tumor markers. One patient had abnormal tumor markers with no evidence of recurrence on MRI until 6 months later. We conclude that in patients with marker-positive CNS germ cell tumors who achieve complete remission, continued surveillance imaging in addition to measurement of tumor markers is indicated to detect recurrences.
PMID: 27406584
ISSN: 1573-7373
CID: 2180172
Pilocytic astrocytoma and glioneuronal tumor with histone H3 K27M mutation [Letter]
PMCID:4983033
PMID: 27519587
ISSN: 2051-5960
CID: 2218812
Consensus paper on post-operative pediatric cerebellar mutism syndrome: the Iceland Delphi results
INTRODUCTION: Confusion has surrounded the description of post-operative mutism and associated morbidity in pediatric patients with cerebellar tumors for years. The heterogeneity of definitions and diagnostic features has hampered research progress within the field, and to date, no international guidelines exist on diagnosis, prevention, treatment, or follow-up of this debilitating condition. An international group of clinicians and researchers from multiple relevant disciplines recently formed a cohesive panel to formulate a new working definition and agree upon standardized methods for diagnosis and follow-up. METHODS: Consensus was obtained using the modified nominal group technique, involving four rounds of online Delphi questionnaires interspersed with a structured consensus conference with lectures, group work, and open discussion sessions. RESULTS: A new, proposed definition of "post-operative pediatric CMS" was formed, preliminary recommendations for diagnostic and follow-up procedures were created, two working groups on a new scoring scale and risk prediction and prevention were established, and areas were identified where further information is needed. DISCUSSION: The consensus process was motivated by desire to further research and improve quality of life for pediatric brain tumor patients. The Delphi rounds identified relevant topics and established basic agreement, while face-to-face engagement helped resolve matters of conflict and refine terminology. The new definition is intended to provide a more solid foundation for future clinical and research work. It is thought as a consensus for moving forward and hopefully paves the way to developing a standard approach to this challenging problem with the advent of better scoring methods and ultimate goal of reducing the risk of CMS.
PMID: 27142103
ISSN: 1433-0350
CID: 2101192
STRATEGIES FOR THE SURGICAL MANAGEMENT OF PEDIATRIC OPTIC PATHWAY GLIOMAS - EXPERIENCE WITH 100 PATIENTS [Meeting Abstract]
ISI:000379749000377
ISSN: 1522-8517
CID: 2964242
SUBGROUP-SPECIFIC OUTCOMES OF CHILDREN WITH MALIGNANT CHILDHOOD BRAIN TUMORS TREATED WITH AN IRRADIATION-SPARING PROTOCOL [Meeting Abstract]
ISI:000379749000695
ISSN: 1522-8517
CID: 2964192
Journal of neuropathology & experimental neurology. 2016:Conference:(92nd):593-594.DOI: 10.1093/jnen/nlw038
Endothelium-independent primitive myxoid vascularization creates invertebrate-like channels to maintain blood supply in optic gliomas [Meeting Abstract]
INTRODUCTION: Optic gliomas are classified as pilocytic astrocytoma (PA) or pilomyxoid astrocytoma (PMXA). Abundant bluish chondroid myxoid matrix is characteristic of PMXA but not PA. We sought to investigate the molecular composition of myxoid matrix and its biologic role in angiogenesis of optic gliomas. We reviewed clinical and pathological data on a cohort of 120 patients with optic glioma diagnosed at NYU Langone Medical Center from 1996 to 2014. We analyzed microvascular density (MVD), perfusion, hypoxia and proliferation by immunohistochemistry and ultrastructural features by electron microscopy. To identify the composition of the myxoid matrix in PMXA we performed liquid chromatography-mass spectrometry (LC-MS) without sample fractionation quantified using peptide spectral counts. PMXA showed significantly lower MVD by CD34 (8.1 vs 14.5, p-value < 0.002) and Erg (7 vs. 13.6, p-value 0.003) than PA, however GLUT-1 showed equal perfusion. Electron microscopy showed that PMXA contain both regular blood vessels with endothelial lining and channels completely lacking endothelial and smooth muscle cells. LC-MS stratified optic gliomas into three distinct groups. We identified 5389 proteins of which 188 were differentially expressed in the three groups (p<0.05, Benjamini-Hochberg adjustment). Between PA and PMXA, we found that most of differentially expressed proteins (146/188) displayed a positive fold change (increasing in PMXA relative to PA), and a minority (42/188) showed a negative fold change. The most abundant extracellular matrix proteins were a chondroitin sulfate proteoglycan versican (VCAN 3.7-fold increase Q=0.000463) and its paralog vertebrate Hyaluronan And Proteoglycan Link Protein 1 (HAPLN1, 22-fold increase from the PA to the PMXA group Q=4.60x10-7). Optic gliomas can develop endothelium-independent channels reminiscent of those in invertebrates to maintain blood supply. The myxoid matrix is composed of VCAN and its linking paralog HAPLN1. Targeting the myxoid matrix may provide novel avenues for therapy of optic gliom
EMBASE:622711609
ISSN: 1554-6578
CID: 3188352
Strategies for the surgical management of pediatric optic pathway gliomas-experience with 100 patients [Meeting Abstract]
Introduction: Pediatric optic pathway gliomas (OPGs) are often considered benign, but can have detrimental effects on the quality of life, impair vision and are a potentially lethal disease. The aim of this study is to report the characteristics and outcomes of surgically treated pediatric OPGs and to identify candidates for different treatment strategies. Methods: Retrospective chart review of consecutive pediatric patients with surgically treated OPGs by a single surgeon at our institution from 1985-2015. Three treatment pathways were defined: (1) surgery without planned adjuvant therapy; (2) surgery with planned adjuvant therapy; and, (3) patients with prior treatment.Results: 100 patients-55 male and 45 female-were included in analysis. 8 patients had NF1. Pathology revealed pilocytic astrocytoma (45%), pilomyxoid astrocytoma (9%), ganglioglioma (3%), and unknown (35%). Radiologic location of the tumor was: hypothalamic 86%, involvement of only chiasm and/or tract in 12%. Median age at diagnosis was 4 years, median age at surgery was 6 years, and median time from diagnosis to surgery was 1 year. Pathway 1: 39 patients; median PFS 73+17 months; OS rate 74%; median follow-up 117 months. Pathway 2: 10 patients; median PFS 29+15 months; OS rate 70%; median follow-up 59 months. Pathway 3: 51 patients; median PFS 33+8 months; OS rate 80%; median follow-up was 73 months. Conclusion: The role of surgery in the treatment of pediatric OPGs depends on patient characteristics and tumor biology. With the adequate therapeutic strategy, long-term PFS and OS can be achieved
EMBASE:611934154
ISSN: 1523-5866
CID: 2258952
Divergent clonal selection dominates medulloblastoma at recurrence
The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (<5%). Whole-genome sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (<12% diagnostic events were retained at recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy.
PMCID:4936195
PMID: 26760213
ISSN: 1476-4687
CID: 1912632
BRAF alteration status and the histone H3F3A gene K27M mutation segregate spinal cord astrocytoma histology
PMCID:4698284
PMID: 26487540
ISSN: 1432-0533
CID: 1810512
Endoscopic resection of solid intraventricular tumors in children [Meeting Abstract]
Objective: We report the feasibility and outcomes of endoscopic resection of select intraventricular tumors in children. Methods: The clinical characteristics of 11 children with solid intraventricular tumors who underwent tumor resection were reviewed. 12 procedures were performed. Results: Gross total resection was achieved in 11 of 12 cases (92%). Maximal diameter ranged from 9-26 mm (mean 16.6 mm). Pathology included subependymal giant cell astrocytomas (SEGA), ependymomas, non-germinomatous germ cell tumor (NGGCT) and pilocytic astrocytoma. Mean follow-up was 35 months (range 10-109 months). All patients returned to their neurological baseline following surgery. Local tumor recurrence occurred in one patient and distant recurrence in another. Complications occurred in one patient, no permanent morbidity or mortality occurred. Hydrocephalus was present preoperatively in 5 cases and was treated with tumor removal alone or with additional endoscopic third ventriculostomy. No patient required a ventriculoperitoneal shunt. Conclusion: Neuroendoscopic gross-total resection of solid intraventricular tumors is a safe procedure in carefully selected pediatric patients
EMBASE:72187571
ISSN: 0256-7040
CID: 1950582
