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      Magnetic resonance spectroscopic imaging in gliomas: clinical diagnosis and radiotherapy planning

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          Abstract

          The reprogramming of cellular metabolism is a hallmark of cancer diagnosis and prognosis. Proton magnetic resonance spectroscopic imaging (MRSI) is a non-invasive diagnostic technique for investigating brain metabolism to establish cancer diagnosis and IDH gene mutation diagnosis as well as facilitate pre-operative planning and treatment response monitoring. By allowing tissue metabolism to be quantified, MRSI provides added value to conventional MRI. MRSI can generate metabolite maps from a single volume or multiple volume elements within the whole brain. Metabolites such as NAA, Cho and Cr, as well as their ratios Cho:NAA ratio and Cho:Cr ratio, have been used to provide tumor diagnosis and aid in radiation therapy planning as well as treatment assessment. In addition to these common metabolites, 2-hydroxygluterate (2HG) has also been quantified using MRSI following the recent discovery of IDH mutations in gliomas. This has opened up targeted drug development to inhibit the mutant IDH pathway. This review provides guidance on MRSI in brain gliomas, including its acquisition, analysis methods, and evolving clinical applications.

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          Ahmedin Jemal, Lindsey A Torre, Rebecca Siegel … (2018)
          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary.

            Paul Kleihues, Otmar D. Wiestler, Guido Reifenberger … (2016)
            The 2016 World Health Organization Classification of Tumors of the Central Nervous System is both a conceptual and practical advance over its 2007 predecessor. For the first time, the WHO classification of CNS tumors uses molecular parameters in addition to histology to define many tumor entities, thus formulating a concept for how CNS tumor diagnoses should be structured in the molecular era. As such, the 2016 CNS WHO presents major restructuring of the diffuse gliomas, medulloblastomas and other embryonal tumors, and incorporates new entities that are defined by both histology and molecular features, including glioblastoma, IDH-wildtype and glioblastoma, IDH-mutant; diffuse midline glioma, H3 K27M-mutant; RELA fusion-positive ependymoma; medulloblastoma, WNT-activated and medulloblastoma, SHH-activated; and embryonal tumour with multilayered rosettes, C19MC-altered. The 2016 edition has added newly recognized neoplasms, and has deleted some entities, variants and patterns that no longer have diagnostic and/or biological relevance. Other notable changes include the addition of brain invasion as a criterion for atypical meningioma and the introduction of a soft tissue-type grading system for the now combined entity of solitary fibrous tumor / hemangiopericytoma-a departure from the manner by which other CNS tumors are graded. Overall, it is hoped that the 2016 CNS WHO will facilitate clinical, experimental and epidemiological studies that will lead to improvements in the lives of patients with brain tumors.
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              Cancer-associated IDH1 mutations produce 2-hydroxyglutarate.

              Lenny Dang, David W White, Stefan Gross … (2009)
              Mutations in the enzyme cytosolic isocitrate dehydrogenase 1 (IDH1) are a common feature of a major subset of primary human brain cancers. These mutations occur at a single amino acid residue of the IDH1 active site, resulting in loss of the enzyme's ability to catalyse conversion of isocitrate to alpha-ketoglutarate. However, only a single copy of the gene is mutated in tumours, raising the possibility that the mutations do not result in a simple loss of function. Here we show that cancer-associated IDH1 mutations result in a new ability of the enzyme to catalyse the NADPH-dependent reduction of alpha-ketoglutarate to R(-)-2-hydroxyglutarate (2HG). Structural studies demonstrate that when arginine 132 is mutated to histidine, residues in the active site are shifted to produce structural changes consistent with reduced oxidative decarboxylation of isocitrate and acquisition of the ability to convert alpha-ketoglutarate to 2HG. Excess accumulation of 2HG has been shown to lead to an elevated risk of malignant brain tumours in patients with inborn errors of 2HG metabolism. Similarly, in human malignant gliomas harbouring IDH1 mutations, we find markedly elevated levels of 2HG. These data demonstrate that the IDH1 mutations result in production of the onco-metabolite 2HG, and indicate that the excess 2HG which accumulates in vivo contributes to the formation and malignant progression of gliomas.
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                Author and article information

                Contributors
                Sunitha B Thakur
                Journal
                Journal ID (nlm-ta): BJR Open
                Journal ID (iso-abbrev): BJR Open
                Journal ID (publisher-id): bjro
                Title: BJR Open
                Publisher: The British Institute of Radiology.
                ISSN (Electronic): 2513-9878
                Publication date Collection: 2020
                Publication date (Electronic): 6 April 2020
                Volume: 2
                Issue: 1
                Electronic Location Identifier: 20190026
                Affiliations
                [1 ]org-divisionDepartment of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave , New York, NY 10065, USA
                [2 ]org-divisionDepartment of Radiology, Humanitas Research Hospital, Via Alessandro Manzoni 56, 20089 , Rozzano, MI, Italy
                [3 ] [3 ]org-divisionDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Ave , New York, NY 10065, USA
                [4 ] [4 ]org-divisionDepartment of Medical Physics, Memorial Sloan Kettering Cancer Center, 300E 66th Street , New York, NY 10065, USA
                [5 ]org-divisionDepartment of Radiology, University of Cagliari, 40 Via Università , 09124 Cagliari, Italy
                [6 ]org-divisionDepartment of Imaging, A.C.Camargo Cancer Center , São Paulo SP, Brazil
                Author notes
                Address correspondence to: Sunitha B Thakur. E-mail: thakurs@ 123456mskcc.org
                Article
                Publisher-manuscript ID: bjro.20190026
                DOI: 10.1259/bjro.20190026
                PMC ID: 7594883
                PubMed ID: 33178960
                SO-VID: 2bee68c3-2cf1-43e1-b95f-3719136d7bc3
                Copyright © © 2020 The Authors. Published by the British Institute of Radiology
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 05 June 2019
                Date revision received : 13 January 2020
                Date accepted : 18 March 2020
                Page count
                Figures: 6, References: 85, Words: 9702
                Categories
                Subject: Review Article
                Compound subject: bjro, BJRO

                Data availability:

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