Elsevier

The Lancet Neurology

Volume 4, Issue 11, November 2005, Pages 760-770
The Lancet Neurology

Review
Low-grade gliomas: an update on pathology and therapy

https://doi.org/10.1016/S1474-4422(05)70222-2Get rights and content

Summary

Low-grade gliomas (LGG) are not benign neoplasms. Patients with LGG eventually die as a consequence of this disease. Although the survival of patients with LGG is better than that of patients with higher-grade tumours, many of the treatments can produce or contribute to chronic impairment, particularly radiotherapy. Chemotherapy has emerged as a promising therapy, although definitive findings are awaited. Breakthroughs in molecular biology have improved our understanding of tumours and have led to the development of novel treatments and better prognoses. Ongoing clinical trials will help to elucidate the optimum management of patients with LGG.

Introduction

Low-grade gliomas (LGG) present a substantial challenge to neuro-oncologists and neurosurgeons. Although more indolent than their high-grade counterparts, they are associated with neurological disability and are fatal. Prognosis is variable; high-risk and low-risk groups have been identified through risk stratification of clinical, tumour, and pathological factors. Optimum treatment is unknown, and the treatment methods routinely used are associated with substantial morbidity. Advances in molecular biology are promising, although more basic and clinical research is needed.

Section snippets

Epidemiology

LGG are a group of tumours with distinct clinical, histological, and molecular characteristics. The WHO classification system classifies tumours by predominant cell type and grade.1 Although it is accepted that all grade I and II lesions are low-grade, the clinical diversity of these tumours detracts from a meaningful classification (table 1). A more clinically informative definition of LGG includes only grade II oligodendrogliomas, astocytomas, and oligoastrocytomas, tumours with similar

Neuroimaging

Diagnosis of LGG requires neuroimaging (figure 1). LGG are shown on CT scanning as isointense to hypointense. Evidence of haemorrhage and calcification might be more common in oligodendroglial tumours. On T2-weighted MRI, LGG are hyperintense and either diffuse with indistinct borders or focal with well-circumscribed margins.9 The epicentre of the astrocytoma is typically within the white matter whereas oligodendrogliomas may be more superficial, occasionally expanding the involved gyrus.

Neuropathology

Pathological criteria for distinguishing low-grade astrocytoma, oligodendroglioma, and oligoastrocytomas are controversial. Oligodendroglial tumours, either pure or mixed with an astrocytic component, were once thought to be rare. Over the past decade, however, they have been diagnosed at a much greater rate. Concomitantly, the incidence of low-grade astrocytomas has declined. Oligodendroglial tumours are more responsive to treatment than astrocytomas and are associated with a better prognosis.

Prognostic factors

Although LGG seem more indolent than high-grade gliomas, they are not benign and eventually prove fatal. Extraneural metastases of LGG are rare. Neoplastic cells, however, can infiltrate surrounding brain. Tumour cells acquire genetic defects which result in anaplastic transformation to a high-grade lesion, and 50–70% of lesions are high grade at the time of tumour progression.5, 12, 49 The clinical effects of LGG are variable, with survival ranging from less than 2 years to more than 10 years.

Surgery

Surgery has long been important in the diagnosis and treatment of LGG. Although the presence of a non-enhancing mass lesion on imaging suggests LGG, about 30% of such lesions are higher grade than predicted by imaging, particularly those in old patients.66, 67 At a minimum, stereotactic biopsy is required to establish diagnosis, although timing is debatable. A neurosurgeon using image guidance can precisely target a radiographic abnormality via a burr hole to sample a lesion without exposing

The future

Many issues are unresolved in the management of LGG. Chemotherapy is emerging as an alternative to radiotherapy as a neoadjuvant treatment. Whether chemotherapy is more effective than up-front radiotherapy is unknown, as is optimum timing of intervention. Ideally, risk stratification from clinical, radiographic, and tumour factors would identify patients who would benefit from early treatment. Although this approach is used in practice, it has yet to be proven. Molecular markers may allow

Search strategy and selection criteria

We identified references by searching MEDLINE (1966 to 2005) in March 2005 for “low-grade glioma”, “radiotherapy”, “chemotherapy”, “surgery”, and “molecular genetics”. Although all studies that included patients treated after the introduction of CT were considered, preference was given to studies published after 1995 and to prospective studies. Only studies published in English and focusing on LGG were considered. References were also identified from relevant articles and through searches

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