Radiation Therapy and Adjuvant Chemotherapy in a Patient With a Malignant Glioneuronal Tumor and Underlying Ataxia Telangiectasia: A Case Report and Review of the Literature

DeWire, Mariko; Beltran, Chris; Boop, Frederick A.; Helton, Kathleen J.; Ellison, David W.; McKinnon, Peter J.; Gajjar, Amar; Panandiker, Atmaram S. Pai

doi:10.1200/jco.2011.40.1430

Cited by 15 publications

(5 citation statements)

References 22 publications

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“…X-ray exposure should be limited to times when it is medically necessary for diagnostic purposes. Radiation therapy for cancer or any other reason is generally harmful for individuals with A-T and should be performed only in rare circumstances and at reduced doses [55, 56]. Although A-T cells in culture have an altered DNA damage response to other genotoxic agents (e.g.…”

Section: Introductionmentioning

confidence: 99%

Ataxia telangiectasia: a review

Rothblum-Oviatt

Wright²,

Lefton‐Greif

et al. 2016

Orphanet J Rare Dis

469

488

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Definition of the diseaseAtaxia telangiectasia (A-T) is an autosomal recessive disorder primarily characterized by cerebellar degeneration, telangiectasia, immunodeficiency, cancer susceptibility and radiation sensitivity. A-T is often referred to as a genome instability or DNA damage response syndrome.EpidemiologyThe world-wide prevalence of A-T is estimated to be between 1 in 40,000 and 1 in 100,000 live births.Clinical descriptionA-T is a complex disorder with substantial variability in the severity of features between affected individuals, and at different ages. Neurological symptoms most often first appear in early childhood when children begin to sit or walk. They have immunological abnormalities including immunoglobulin and antibody deficiencies and lymphopenia. People with A-T have an increased predisposition for cancers, particularly of lymphoid origin. Pulmonary disease and problems with feeding, swallowing and nutrition are common, and there also may be dermatological and endocrine manifestations.EtiologyA-T is caused by mutations in the ATM (Ataxia Telangiectasia, Mutated) gene which encodes a protein of the same name. The primary role of the ATM protein is coordination of cellular signaling pathways in response to DNA double strand breaks, oxidative stress and other genotoxic stress.DiagnosisThe diagnosis of A-T is usually suspected by the combination of neurologic clinical features (ataxia, abnormal control of eye movement, and postural instability) with one or more of the following which may vary in their appearance: telangiectasia, frequent sinopulmonary infections and specific laboratory abnormalities (e.g. IgA deficiency, lymphopenia especially affecting T lymphocytes and increased alpha-fetoprotein levels). Because certain neurological features may arise later, a diagnosis of A-T should be carefully considered for any ataxic child with an otherwise elusive diagnosis. A diagnosis of A-T can be confirmed by the finding of an absence or deficiency of the ATM protein or its kinase activity in cultured cell lines, and/or identification of the pathological mutations in the ATM gene.Differential diagnosisThere are several other neurologic and rare disorders that physicians must consider when diagnosing A-T and that can be confused with A-T. Differentiation of these various disorders is often possible with clinical features and selected laboratory tests, including gene sequencing.Antenatal diagnosisAntenatal diagnosis can be performed if the pathological ATM mutations in that family have been identified in an affected child. In the absence of identifying mutations, antenatal diagnosis can be made by haplotype analysis if an unambiguous diagnosis of the affected child has been made through clinical and laboratory findings and/or ATM protein analysis.Genetic counselingGenetic counseling can help family members of a patient with A-T understand when genetic testing for A-T is feasible, and how the test results should be interpreted.Management and prognosisTreatment of the neurologic problems associated wit...

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Section: Introductionmentioning

confidence: 99%

Ataxia telangiectasia: a review

Rothblum-Oviatt

Wright²,

Lefton‐Greif

et al. 2016

Orphanet J Rare Dis

469

488

View full text Add to dashboard Cite

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“…Treatment options that include surgical resection extent, radiation therapy and chemotherapy are varied and unstandardized. Moreover, the results of each treatment are too heterogeneous and it is impossible to assume the OS or PFS ( Table 3 ) 1 2 4 8 13 16 19 21 22) . Although those tumors generally have a more favorable prognosis than glioblastomas 22) , the present median OS of 21.2 months and PFS of 6.3 months of patients with the pathological diagnosis were not so favorable.…”

Section: Discussionmentioning

confidence: 99%

Malignant Glioma with Neuronal Marker Expression : A Clinicopathological Study of 18 Cases

Kim

Lee

et al. 2015

J Korean Neurosurg Soc

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ObjectiveMalignant gliomas with neuronal marker expression (MGwNM) are rare and poorly characterized. Increasingly diverse types of MGwNM have been described and these reported cases underscore the dilemmas in the classification and diagnosis of those tumors. The aim of this study is to provide additional insights into MGwNM and present the clinicopathological features of 18 patients.MethodsWe reviewed the medical records of 18 patients diagnosed as MGwNM at our institute between January 2006 and December 2012. Macroscopic total resection was performed in 11 patients (61%). We evaluated the methylation status of O6-methylguanine-DNA methyltransferase (MGMT) and expression of isocitrate dehydrogenase 1 (IDH-1) in all cases, and deletions of 1p and 19q in available cases.ResultsThe estimated median overall survival was 21.2 months. The median progression-free survival was 6.3 months. Six patients (33%) had MGMT methylation but IDH1 mutation was found in only one patient (6%). Gene analysis for 1p19q performed in nine patients revealed no deletion in six, 19q deletion only in two, and 1p deletion only in one. The extent of resection was significantly correlated with progression free survival on both univariate analysis and multivariate analysis (p=0.002 and p=0.013, respectively).ConclusionIn this study, the overall survival of MGwNM was not superior to glioblastoma. The extent of resection has a significant prognostic impact on progression-free survival. Further studies of the prognostic factors related to chemo-radio therapy, similar to studies with glioblastoma, are mandatory to improve survival.

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“…need, and disease control can be achieved with doses of approximately one-third of those prescribed in typical schedules 91,92 (Supplementary Table 1). Other known rare genetic syndromes associated with homozygous germline mutations in genes involved in DDR that lead to increased cellular and clinical radiosensitivity, risk of toxicity and radiosusceptibility have been reviewed elsewhere 93 .…”

Section: Review Articlementioning

confidence: 99%

Predicting tumour radiosensitivity to deliver precision radiotherapy

2022

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Owing to advances in radiotherapy, the physical properties of radiation can be optimized to enable individualized treatment; however, optimization is rarely based on biological properties and, therefore, treatments are generally planned with the assumption that all tumours respond similarly to radiation. Radiation affects multiple cellular pathways, including DNA damage, hypoxia, proliferation, stem cell phenotype and immune response. In this Review, we summarize the effect of these pathways on tumour responses to radiotherapy and the current state of research on genomic classifiers designed to exploit these variations to inform treatment decisions. We also discuss whether advances in genomics have generated evidence that could be practice changing and whether advances in genomics are now ready to be used

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Radiation Therapy and Adjuvant Chemotherapy in a Patient With a Malignant Glioneuronal Tumor and Underlying Ataxia Telangiectasia: A Case Report and Review of the Literature

Cited by 15 publications

References 22 publications

Ataxia telangiectasia: a review

Ataxia telangiectasia: a review

Malignant Glioma with Neuronal Marker Expression : A Clinicopathological Study of 18 Cases

Predicting tumour radiosensitivity to deliver precision radiotherapy

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