Early aging in adult survivors of childhood medulloblastoma: long-term neurocognitive, functional, and physical outcomes.

Abstract:

:Treatment for medulloblastoma during childhood impairs neurocognitive function in survivors. While those diagnosed at younger ages are most vulnerable, little is known about the long-term neurocognitive, functional, and physical outcomes in survivors as they approach middle age. In this retrospective cohort study, we assessed 20 adults who were treated with surgery and radiotherapy for medulloblastoma during childhood (median age at assessment, 21.9 years [range, 18-47 years]; median time since diagnosis, 15.5 years [range, 6.5-42.2 years]). Nine patients also underwent chemotherapy. Cross-sectional analyses of current neurocognitive, functional, and physical status were conducted. Data from prior neuropsychological assessments were available for 18 subjects; longitudinal analyses were used to model individual change over time for those subjects. The group was well below average across multiple neurocognitive domains, and 90% had required accommodations at school for learning disorders. Longer time since diagnosis, but not age at diagnosis, was associated with continued decline in working memory, a common sign of aging. Younger age at diagnosis was associated with lower intelligence quotient and academic achievement scores, even many years after treatment had been completed. The most common health complications in survivors were hearing impairment, second cancers, diabetes, hypertension, and endocrine deficiencies. Adult survivors of childhood medulloblastoma exhibit signs of early aging regardless of how young they were at diagnosis. As survival rates for brain tumors continue to improve, these neurocognitive and physical sequelae may become evident in survivors diagnosed at different ages across the lifespan. It will become increasingly important to identify factors that contribute to risk and resilience in this growing population.

journal_name

Neuro Oncol

journal_title

Neuro-oncology

authors

Edelstein K,Spiegler BJ,Fung S,Panzarella T,Mabbott DJ,Jewitt N,D'Agostino NM,Mason WP,Bouffet E,Tabori U,Laperriere N,Hodgson DC

doi

10.1093/neuonc/nor015

subject

Has Abstract

pub_date

2011-05-01 00:00:00

pages

536-45

issue

5

eissn

1522-8517

issn

1523-5866

pii

nor015

journal_volume

13

pub_type

杂志文章
  • Apparent diffusion coefficient histogram metrics correlate with survival in diffuse intrinsic pontine glioma: a report from the Pediatric Brain Tumor Consortium.

    abstract:BACKGROUND:Diffuse intrinsic pontine glioma (DIPG) is associated with poor survival regardless of therapy. We used volumetric apparent diffusion coefficient (ADC) histogram metrics to determine associations with progression-free survival (PFS) and overall survival (OS) at baseline and after radiation therapy (RT). MET...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nov256

    authors: Poussaint TY,Vajapeyam S,Ricci KI,Panigrahy A,Kocak M,Kun LE,Boyett JM,Pollack IF,Fouladi M

    更新日期:2016-05-01 00:00:00

  • Glutathione S-transferase M1 and T1 polymorphisms may predict adverse effects after therapy in children with medulloblastoma.

    abstract::Glutathione S-transferases (GSTs) are polymorphic enzymes that catalyze the glutathione conjugation of alkylating agents, platinum compounds, and free radicals formed by radiation used to treat medulloblastoma. We hypothesized that GST polymorphisms may be responsible, in part, for individual differences in toxicity a...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/15228517-2008-089

    authors: Barahmani N,Carpentieri S,Li XN,Wang T,Cao Y,Howe L,Kilburn L,Chintagumpala M,Lau C,Okcu MF

    更新日期:2009-06-01 00:00:00

  • Myeloablative chemotherapy for recurrent aggressive oligodendroglioma.

    abstract::The objective of this study was to ascertain the duration of tumor control and the toxicities of dose-intense myeloablative chemotherapy for patients with recurrent oligodendrogliomas. Patients with previously irradiated oligodendrogliomas, either pure or mixed, that were contrast enhancing, measurable, and behaving a...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/2.2.114

    authors: Cairncross G,Swinnen L,Bayer R,Rosenfeld S,Salzman D,Paleologos N,Kaminer L,Forsyth P,Stewart D,Peterson K,Hu W,Macdonald D,Ramsay D,Smith A,Oligodendroglioma Study Group.

    更新日期:2000-04-01 00:00:00

  • Fractional anisotropy of the optic radiations is associated with visual acuity loss in optic pathway gliomas of neurofibromatosis type 1.

    abstract:BACKGROUND:No more than half of patients with neurofibromatosis type 1 (NF1)-associated optic pathway gliomas (OPGs) develop vision loss. Prospectively identifying those who will require therapy remains challenging, because no reliable factors have yet been identified that predict future vision loss. To determine wheth...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/not068

    authors: de Blank PM,Berman JI,Liu GT,Roberts TP,Fisher MJ

    更新日期:2013-08-01 00:00:00

  • Integration of 2-hydroxyglutarate-proton magnetic resonance spectroscopy into clinical practice for disease monitoring in isocitrate dehydrogenase-mutant glioma.

    abstract:BACKGROUND:The majority of WHO grades II and III gliomas harbor a missense mutation in the metabolic gene isocitrate dehydrogenase (IDH) and accumulate the metabolite R-2-hydroxyglutarate (R-2HG). Prior studies showed that this metabolite can be detected in vivo using proton magnetic-resonance spectroscopy (MRS), but t...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nov307

    authors: de la Fuente MI,Young RJ,Rubel J,Rosenblum M,Tisnado J,Briggs S,Arevalo-Perez J,Cross JR,Campos C,Straley K,Zhu D,Dong C,Thomas A,Omuro AA,Nolan CP,Pentsova E,Kaley TJ,Oh JH,Noeske R,Maher E,Choi C,Gutin PH,Ho

    更新日期:2016-02-01 00:00:00

  • PARP mediated PARylation of MGMT is critical to promote repair of temozolomide-induced O6-methylguanine DNA damage in glioblastoma.

    abstract:BACKGROUND:Temozolomide (TMZ) resistance in Glioblastoma (GBM) is mediated by the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). MGMT promoter methylation (occurs in about 40% patients) is associated with loss of MGMT expression (MGMT-) that compromises DNA repair, leading to a favorable response to ...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noab003

    authors: Wu S,Li X,Gao F,de Groot JF,Koul D,Yung WKA

    更新日期:2021-01-12 00:00:00

  • Diffusion radiomics as a diagnostic model for atypical manifestation of primary central nervous system lymphoma: development and multicenter external validation.

    abstract:Background:Radiomics is a rapidly growing field in neuro-oncology, but studies have been limited to conventional MRI, and external validation is critically lacking. We evaluated technical feasibility, diagnostic performance, and generalizability of a diffusion radiomics model for identifying atypical primary central ne...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,多中心研究

    doi:10.1093/neuonc/noy021

    authors: Kang D,Park JE,Kim YH,Kim JH,Oh JY,Kim J,Kim Y,Kim ST,Kim HS

    更新日期:2018-08-02 00:00:00

  • Generation of diffuse intrinsic pontine glioma mouse models by brainstem-targeted in utero electroporation.

    abstract:BACKGROUND:Diffuse intrinsic pontine gliomas (DIPGs) are highly lethal childhood brain tumors. Their unique genetic makeup, pathological heterogeneity, and brainstem location all present challenges to treatment. Developing mouse models that accurately reflect each of these distinct features will be critical to advance ...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noz197

    authors: Patel SK,Hartley RM,Wei X,Furnish R,Escobar-Riquelme F,Bear H,Choi K,Fuller C,Phoenix TN

    更新日期:2020-03-05 00:00:00

  • Survey of treatment recommendations for anaplastic oligodendroglioma.

    abstract::Anaplastic oligodendroglioma is a malignant brain tumor uniquely sensitive to treatment with both chemotherapy and radiotherapy. There are few prospective clinical trials for newly diagnosed patients and multiple approaches to the treatment of these patients. This study explored the recommended treatment offered by ex...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/15228517-2007-002

    authors: Abrey LE,Louis DN,Paleologos N,Lassman AB,Raizer JJ,Mason W,Finlay J,MacDonald DR,DeAngelis LM,Cairncross JG,Oligodendroglioma Study Group.

    更新日期:2007-07-01 00:00:00

  • SPARC affects glioma cell growth differently when grown on brain ECM proteins in vitro under standard versus reduced-serum stress conditions.

    abstract::Secreted protein acidic and rich in cysteine (SPARC) has a suppressive effect on U87 glioma cell proliferation when assessed in vitro and in vivo using parental U87T2 and U87T2-derived SPARC-transfected clones. Since SPARCinteracts with extracellular matrix (ECM) proteins, we examined the effect of SPARC secretion on ...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/5.4.244

    authors: Vadlamuri SV,Media J,Sankey SS,Nakeff A,Divine G,Rempel SA

    更新日期:2003-10-01 00:00:00

  • Dogs are man's best friend: in sickness and in health.

    abstract::With the median survival of 14.6 months following best available standard of care, malignant gliomas (MGs) remain one of the biggest therapeutic challenges of the modern time. Although the last several decades have witnessed tremendous advancement in our understanding of MG and evolution of many successful preclinical...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,评审

    doi:10.1093/neuonc/now109

    authors: Bentley RT,Ahmed AU,Yanke AB,Cohen-Gadol AA,Dey M

    更新日期:2017-03-01 00:00:00

  • Effect of valproic acid on seizure control and on survival in patients with glioblastoma multiforme.

    abstract:BACKGROUND:To examine the efficacy of valproic acid (VPA) given either with or without levetiracetam (LEV) on seizure control and on survival in patients with glioblastoma multiforme (GBM) treated with chemoradiation. METHODS:A retrospective analysis was performed on 291 patients with GBM. The efficacies of VPA and LE...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/not057

    authors: Kerkhof M,Dielemans JC,van Breemen MS,Zwinkels H,Walchenbach R,Taphoorn MJ,Vecht CJ

    更新日期:2013-07-01 00:00:00

  • A phase II trial of primary temozolomide in patients with grade III oligodendroglial brain tumors.

    abstract::Glial tumors with oligodendroglial components are considered chemo-responsive. Forty newly diagnosed patients (11 anaplastic oligodendrogliomas [OD] and 29 anaplastic oligoastrocytomas [OA]) were enrolled into this multicenter, open-label, single-arm Phase II trial of first-line temozolomide (200 mg/m(2) on days 1-5 e...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,多中心研究

    doi:10.1093/neuonc/nop065

    authors: Gan HK,Rosenthal MA,Dowling A,Kalnins R,Algar E,Wong N,Benson A,Woods AM,Cher L

    更新日期:2010-05-01 00:00:00

  • Phase I study of 5-fluorouracil in children and young adults with recurrent ependymoma.

    abstract:BACKGROUND:We report a phase I study to examine the pharmacokinetics, safety, and recommended dosage of weekly intravenous bolus 5-fluorouracil (5-FU) in children and young adults with recurrent ependymoma. METHODS:Patients 22 years of age or less with recurrent ependymoma were treated with bolus dosage 5-FU weekly fo...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nov181

    authors: Wright KD,Daryani VM,Turner DC,Onar-Thomas A,Boulos N,Orr BA,Gilbertson RJ,Stewart CF,Gajjar A

    更新日期:2015-12-01 00:00:00

  • Glioblastoma stem cell differentiation into endothelial cells evidenced through live-cell imaging.

    abstract:Background:Glioblastoma cell-initiated vascularization is an alternative angiogenesis called vasculogenic mimicry. However, current knowledge on the mechanism of de novo vessel formation from glioblastoma stem cells (GSCs) is limited. Methods:Sixty-four glioblastoma samples from patients and 10 fluorescent glioma xeno...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nox016

    authors: Mei X,Chen YS,Chen FR,Xi SY,Chen ZP

    更新日期:2017-08-01 00:00:00

  • Enhanced expression of coproporphyrinogen oxidase in malignant brain tumors: CPOX expression and 5-ALA-induced fluorescence.

    abstract::In photodynamic diagnosis, 5-aminolevulinic acid (5-ALA) is widely used for the fluorescence-guided resection of malignant brain tumors, where 5-ALA is converted to protoporphyrin IX, which exhibits strong fluorescence. Little is known, however, about the detailed molecular mechanisms underlying 5-ALA-induced fluoresc...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,收录出版

    doi:10.1093/neuonc/nor116

    authors: Takahashi K,Ikeda N,Nonoguchi N,Kajimoto Y,Miyatake S,Hagiya Y,Ogura S,Nakagawa H,Ishikawa T,Kuroiwa T

    更新日期:2011-11-01 00:00:00

  • Motexafin gadolinium and involved field radiation therapy for intrinsic pontine glioma of childhood: a Children's Oncology Group phase I study.

    abstract::The purpose of this study was to determine the dose-limiting toxicities, maximum tolerated dose, pharmacokinetics, and intratumor and brain distribution of motexafin gadolinium (MGd) with involved field radiation therapy in children with newly diagnosed intrinsic pontine gliomas. MGd was administered as a 5-min intrav...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/15228517-2008-043

    authors: Bradley KA,Pollack IF,Reid JM,Adamson PC,Ames MM,Vezina G,Blaney S,Ivy P,Zhou T,Krailo M,Reaman G,Mehta MP,Children's Oncology Group.

    更新日期:2008-10-01 00:00:00

  • Rhenium-186 liposomes as convection-enhanced nanoparticle brachytherapy for treatment of glioblastoma.

    abstract::Although external beam radiation is an essential component to the current standard treatment of primary brain tumors, its application is limited by toxicity at doses more than 80 Gy. Recent studies have suggested that brachytherapy with liposomally encapsulated radionuclides may be of benefit, and we have reported met...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nos060

    authors: Phillips WT,Goins B,Bao A,Vargas D,Guttierez JE,Trevino A,Miller JR,Henry J,Zuniga R,Vecil G,Brenner AJ

    更新日期:2012-04-01 00:00:00

  • Recursive partitioning analysis of prognostic variables in newly diagnosed anaplastic oligodendroglial tumors.

    abstract:BACKGROUND:Anaplastic oligodendroglial tumors are rare, and median survival varies widely. Analysis of 1p19q deletion is performed commonly and is an important prognostic factor. However, age and other clinical variables also carry prognostic value, and it is unclear how to incorporate them into clinical decision makin...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nou083

    authors: Panageas KS,Reiner AS,Iwamoto FM,Cloughesy TF,Aldape KD,Rivera AL,Eichler AF,Louis DN,Paleologos NA,Fisher BJ,Ashby LS,Cairncross JG,Urgoiti GB,Wen PY,Ligon KL,Schiff D,Robins HI,Rocque BG,Chamberlain MC,Mason WP,

    更新日期:2014-11-01 00:00:00

  • Immunological responses in a patient with glioblastoma multiforme treated with sequential courses of temozolomide and immunotherapy: case study.

    abstract::Cytotoxic chemotherapy that induces lymphopenia is predicted to ablate the benefits of active antitumor immunization. Temozolomide is an effective chemotherapeutic agent for patients with glioblastoma multiforme, but it induces significant lymphopenia. Although there is monthly fluctuation of the white blood cell coun...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/15228517-2007-046

    authors: Heimberger AB,Sun W,Hussain SF,Dey M,Crutcher L,Aldape K,Gilbert M,Hassenbusch SJ,Sawaya R,Schmittling B,Archer GE,Mitchell DA,Bigner DD,Sampson JH

    更新日期:2008-02-01 00:00:00

  • A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE).

    abstract:BACKGROUND:Ofranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab. METHODS:This pivotal phase III ra...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noz232

    authors: Cloughesy TF,Brenner A,de Groot JF,Butowski NA,Zach L,Campian JL,Ellingson BM,Freedman LS,Cohen YC,Lowenton-Spier N,Rachmilewitz Minei T,Fain Shmueli S,GLOBE Study Investigators.,Wen PY

    更新日期:2020-05-15 00:00:00

  • Endogenous inhibitors of angiogenesis in malignant gliomas: nature's antiangiogenic therapy.

    abstract::Angiogenesis is necessary for tumor growth beyond a volume of approximately 2 mm(3). This observation, along with the accessibility of tumor vessels to therapeutic targeting, has resulted in a research focus on inhibitors of angiogenesis. A number of endogenous inhibitors of angiogenesis are found in the body. Some of...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,评审

    doi:10.1215/S115285170400119X

    authors: Rege TA,Fears CY,Gladson CL

    更新日期:2005-04-01 00:00:00

  • Invasion patterns in brain metastases of solid cancers.

    abstract:BACKGROUND:Brain metastases are generally considered to be well demarcated from the surrounding brain parenchyma, although infiltrative growth patterns have been observed. We systemically investigated infiltration patterns and expression of adhesion molecules in a large and well-defined series of autopsy cases of brain...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/not112

    authors: Berghoff AS,Rajky O,Winkler F,Bartsch R,Furtner J,Hainfellner JA,Goodman SL,Weller M,Schittenhelm J,Preusser M

    更新日期:2013-12-01 00:00:00

  • Tailoring neurophysiological strategies with clinical context enhances resection and safety and expands indications in gliomas involving motor pathways.

    abstract:BACKGROUND:Resection of motor pathway gliomas requires the intraoperative recognition of essential cortical-subcortical motor structures. The degree of involvement of motor structures is variable, and increases as result of treatments patients are submitted to. Intraoperative neurophysiology offers various stimulation ...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/not327

    authors: Bello L,Riva M,Fava E,Ferpozzi V,Castellano A,Raneri F,Pessina F,Bizzi A,Falini A,Cerri G

    更新日期:2014-08-01 00:00:00

  • Feasibility, phase I, and phase II studies of tandutinib, an oral platelet-derived growth factor receptor-β tyrosine kinase inhibitor, in patients with recurrent glioblastoma.

    abstract:Background:Platelet-derived growth factor (PDGF) signaling is important in gliomagenesis and PDGF receptor-β is expressed on most endothelial cells in glioblastoma specimens. Methods:We report the results of feasibility, phase I, and phase II studies of tandutinib (MLN518), an orally bioavailable inhibitor of type III...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,多中心研究

    doi:10.1093/neuonc/now185

    authors: Batchelor TT,Gerstner ER,Ye X,Desideri S,Duda DG,Peereboom D,Lesser GJ,Chowdhary S,Wen PY,Grossman S,Supko JG

    更新日期:2017-04-01 00:00:00

  • Vascular biomarkers derived from dynamic contrast-enhanced MRI predict response of vestibular schwannoma to antiangiogenic therapy in type 2 neurofibromatosis.

    abstract:BACKGROUND:Antiangiogenic therapy of vestibular schwannoma (VS) in type 2 neurofibromatosis can produce tumor shrinkage with response rates of 40%-60%. This study examines the predictive value of parameter-derived MRI in this setting. METHODS:Twelve patients with 20 VSs were recruited. Each had at least one rapidly gr...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nov168

    authors: Li KL,Djoukhadar I,Zhu X,Zhao S,Lloyd S,McCabe M,McBain C,Evans DG,Jackson A

    更新日期:2016-02-01 00:00:00

  • Detection of glioblastoma response to temozolomide combined with bevacizumab based on μMRI and μPET imaging reveals [18F]-fluoro-L-thymidine as an early and robust predictive marker for treatment efficacy.

    abstract::The individualized care of glioma patients ought to benefit from imaging biomarkers as precocious predictors of therapeutic efficacy. Contrast enhanced MRI and [(18)F]-fluorodeoxyglucose (FDG)-PET are routinely used in clinical settings; their ability to forecast the therapeutic response is controversial. The objectiv...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nos260

    authors: Corroyer-Dulmont A,Pérès EA,Petit E,Guillamo JS,Varoqueaux N,Roussel S,Toutain J,Divoux D,MacKenzie ET,Delamare J,Ibazizène M,Lecocq M,Jacobs AH,Barré L,Bernaudin M,Valable S

    更新日期:2013-01-01 00:00:00

  • In vivo efficacy of a novel histone deacetylase inhibitor in combination with radiation for the treatment of gliomas.

    abstract::Histone modification has emerged as a promising approach to cancer therapy. We explored the in vivo efficacy of a butyric acid derivative, pivaloyloxymethyl butyrate (AN-9), for the treatment of gliomas. Relative to control and single-modality treatments, the combination of AN-9 and radiation significantly inhibited t...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/15228517-2006-032

    authors: Entin-Meer M,Yang X,VandenBerg SR,Lamborn KR,Nudelman A,Rephaeli A,Haas-Kogan DA

    更新日期:2007-04-01 00:00:00

  • A single intravenous injection of oncolytic picornavirus SVV-001 eliminates medulloblastomas in primary tumor-based orthotopic xenograft mouse models.

    abstract::Difficulties of drug delivery across the blood-brain barrier (BBB) and failure to eliminate cancer stem cells (CSCs) are believed to be the major causes of tumor recurrences in children with medulloblastoma (MB). Seneca Valley virus-001 (SVV-001) is a naturally occurring oncolytic picornavirus that can be systemically...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noq148

    authors: Yu L,Baxter PA,Zhao X,Liu Z,Wadhwa L,Zhang Y,Su JM,Tan X,Yang J,Adesina A,Perlaky L,Hurwitz M,Idamakanti N,Police SR,Hallenbeck PL,Blaney SM,Chintagumpala M,Hurwitz RL,Li XN

    更新日期:2011-01-01 00:00:00

  • DNA repair after irradiation in glioma cells and normal human astrocytes.

    abstract::We examined DNA damage responses and repair in four human glioma cell lines (A7, U87, T98G, and U373) and normal human astrocytes (NHAs) after clinically relevant radiation doses to establish whether we could identify differences among them that might suggest new approaches to selective radiosensitization. We used pho...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/15228517-2007-030

    authors: Short SC,Martindale C,Bourne S,Brand G,Woodcock M,Johnston P

    更新日期:2007-10-01 00:00:00