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Management of diffuse low-grade gliomas in adults — use of molecular diagnostics

Key Points

  • In the 2016 WHO classification of brain tumours, diffuse gliomas — including grade II gliomas — are defined by both morphological and molecular criteria

  • Prognosis is more closely associated with molecular diagnosis than with morphology, but grade remains prognostically important

  • Immunohistochemistry and cytogenetics provide an accurate diagnosis for most patients, whereas chromosomal and gene arrays provide more complete diagnostic information for some tumours

  • Total resection of all tumour that is visible on MRI without inflicting additional neurological deficit is most common in patients with isocitrate dehydrogenase (IDH)-mutated tumours, and results in increased survival in these patients

  • Although radiation alone and temozolomide alone seem to result in comparable progression-free survival overall in patients with grade II glioma, those with IDH-mutated tumours without 1p/19q codeletion have longer progression-free survival with radiation therapy than with temozolomide

  • Treatment with radiation therapy plus chemotherapy with procarbazine, lomustine and vincristine results in prolongation of survival in most patients, especially those with oligodendroglioma or other IDH-mutated tumours

Abstract

Diffuse WHO grade II gliomas are histologically and genetically heterogeneous. The 2016 WHO classification redefines grade II gliomas with respect to morphological and molecular tumour alterations: grade II oligodendrogliomas are defined by the presence of whole-arm codeletion in chromosomal arms 1p/19q, whereas isocitrate dehydrogenase (IDH) mutations define subclasses of astrocytoma. Although histological grade remains useful, the prognoses of patients with glioma are more tightly associated with molecular alterations than with grade, and chromosomal and gene array technologies are becoming increasingly beneficial in understanding tumour genetic heterogeneity. The indolent nature of the disease often creates subtle neurological symptoms that can be overlooked or misunderstood, resulting in delayed diagnosis. Seizures often herald the diagnosis, especially in patients who have IDH mutations, which are associated with an increased production of 2-hydroxyglutarate. Treatment paradigms have shifted, owing to new diagnostic criteria and new clinical trial evidence. Patients benefit more from chemoradiation than radiation alone, especially those with tumour IDH1 Arg132His mutations; gross total resection of the tumour, including tumours with IDH mutations, is associated with prolonged survival. Initial observation remains appropriate in patients whose rate of disease growth is not yet completely defined; such patients could include those with completely resected disease and those with 1p/19q codeleted tumours.

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Figure 1: Histopathology of low-grade glioma.
Figure 2: Array results for prototypic examples of different adult diffuse gliomas.
Figure 3: Overall survival, according to treatment group.
Figure 4: Progression-free survival, according to treatment group.

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All authors contributed equally to researching data for the article, substantial contribution to discussion of content and writing the article. J.B. reviewed and edited the article before submission.

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Correspondence to Jan Buckner.

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Buckner, J., Giannini, C., Eckel-Passow, J. et al. Management of diffuse low-grade gliomas in adults — use of molecular diagnostics. Nat Rev Neurol 13, 340–351 (2017). https://doi.org/10.1038/nrneurol.2017.54

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