Home 5 Conditions 5 Low-Grade Gliomas

Brain Tumours

Low-Grade Gliomas

A slow-growing primary brain tumour — treatment is individualised and often surgical.

In brief

A slow-growing tumour arising from the brain’s support cells
Corresponds to WHO grade 1 and grade 2 tumours
May cause seizures, or be found incidentally
Molecular markers guide diagnosis and treatment
Managed by monitoring, surgery, and sometimes radiotherapy or chemotherapy

What is a Low-Grade Glioma?

A low-grade glioma (LGG) is a type of primary brain tumour that arises from the glial cells — the supporting cells of the brain. The word “glioma” simply means a tumour of glial origin, and “low-grade” refers to tumours that are slower growing and generally less immediately aggressive than their high-grade counterparts. Low-grade gliomas account for approximately 5% of all primary brain tumours in adults and represent some of the most common brain tumours in younger adults, with IDH-mutant astrocytomas typically presenting in the late 30s and oligodendrogliomas in the mid-40s. It is important to understand that, despite the term “low-grade”, these are serious conditions that require careful ongoing management. Most low-grade gliomas will evolve and become more aggressive over time through a process called malignant transformation — they are not curable in the traditional sense, but with optimal treatment, many patients live for many years and sometimes decades after diagnosis.

How are Low-Grade Gliomas Classified?

The way brain tumours are classified has changed significantly in recent years. The 2021 WHO Classification of Tumours of the Central Nervous System — the most recent international standard — now classifies diffuse gliomas primarily according to their molecular genetic characteristics rather than their appearance under a microscope alone. This shift to molecular diagnosis has fundamentally improved the accuracy of diagnosis, prognosis, and treatment planning.¹ Under the 2021 WHO classification, the principal low-grade diffuse gliomas in adults are:

Astrocytoma, IDH-mutant (WHO Grade 2)

A diffusely infiltrating tumour carrying a mutation in the IDH gene. It typically arises in the frontal or temporal lobe in younger adults. It does not have 1p/19q codeletion. Under the 2021 WHO classification this single tumour type can be grade 2, 3, or 4 — assigned from specific histological and molecular features: grade 2 is the low-grade, slowest-growing form covered by this sheet, whereas grades 3 and 4 are high-grade and behave more aggressively.

Oligodendroglioma, IDH-mutant and 1p/19q-codeleted (WHO Grade 2 or 3)

Defined by the combined presence of an IDH gene mutation and deletion of both chromosomal arms 1p and 19q (1p/19q codeletion). Oligodendrogliomas carry the most favourable prognosis of all diffuse gliomas, with median survival measured in over a decade in many studies. The 1p/19q codeletion is now pathognomonic — that is, the sole defining diagnostic criterion — for this tumour type.²

IDH-wildtype tumours

A small proportion of tumours that appear low-grade under the microscope but lack IDH mutation are classified as IDH-wildtype. These tumours carry a markedly worse prognosis, with a median survival approaching that of a glioblastoma, and are now generally managed more aggressively from the outset.³

Why Do Molecular Markers Matter?

The molecular profile of a low-grade glioma is the single most important factor in determining prognosis and guiding treatment. The key markers are:

IDH mutation (IDH1 or IDH2) — present in over 70% of low-grade gliomas; strongly associated with a more favourable prognosis, longer survival, and better response to chemotherapy. Patients with IDH-mutant tumours and 1p/19q codeletion (oligodendroglioma) have a median survival exceeding 8 years; those with IDH mutation without codeletion (astrocytoma) have a median survival of approximately 6.3 years; those with IDH-wildtype have a markedly shorter survival, approaching that of glioblastoma.³
1p/19q codeletion — pathognomonic for oligodendroglioma; associated with the most favourable prognosis and the best response to PCV chemotherapy. Median survival of patients with 1p/19q-codeleted oligodendroglioma can exceed 12 years in some series.²
CDKN2A/B homozygous deletion — a negative prognostic marker; its presence alone is now sufficient to designate an IDH-mutant astrocytoma as WHO Grade 4.¹
TERT promoter mutation and ATRX loss — two further markers that indicate the direction of classification: loss of ATRX typically points to an astrocytoma, whereas retained (intact) ATRX together with a TERT promoter mutation — in the presence of 1p/19q codeletion — points to an oligodendroglioma.¹

What are the Symptoms of a Low-Grade Glioma?

Because low-grade gliomas grow slowly, symptoms often develop gradually and may be present for months or even years before diagnosis. They can reach a considerable size before symptoms become apparent, and many are initially found as an incidental finding on brain imaging performed for an unrelated reason. The most common presenting symptoms are:

Seizures (epilepsy) — the most common presentation, occurring in approximately 70–90% of patients; seizures can be focal (affecting one part of the body) or generalised (affecting the whole body). The onset of seizures in a young adult without a prior history should always prompt brain imaging.
Headaches — often non-specific; may be related to increased brain pressure or local irritation from the tumour
Focal neurological deficits — weakness, numbness, speech difficulty, or visual changes, depending on the location of the tumour within the brain
Cognitive or personality changes — difficulties with memory, concentration, or behaviour, particularly with frontal lobe tumours

How are Low-Grade Gliomas Diagnosed?

Magnetic Resonance Imaging (MRI)

MRI is the gold standard for identifying and characterising low-grade gliomas. They typically appear as diffuse, poorly demarcated areas of increased signal on specific MRI sequences (T2 and FLAIR). A defining feature is that they characteristically do not take up contrast (gadolinium): a low-grade glioma is typically non-enhancing, and the appearance of new or nodular enhancement is an important warning sign that a tumour is higher-grade or has undergone malignant transformation.⁴ Some low-grade tumours — particularly oligodendrogliomas — can show patchy enhancement without being high-grade, so this feature is interpreted alongside the overall clinical and imaging picture. A characteristic pattern called the “T2-FLAIR mismatch” sign is highly specific for IDH-mutant, 1p/19q non-codeleted astrocytoma. MRI provides essential information about the tumour’s size, location, and relationship to critical brain structures, and guides surgical planning.⁵

Surgical resection or biopsy — Tissue diagnosis

Tissue diagnosis is mandatory for all low-grade gliomas. A definitive diagnosis cannot be made on imaging alone. In most cases the preferred approach is an open craniotomy with maximal safe resection — removing as much of the tumour as can be safely achieved without harming the patient — which both provides tissue for diagnosis and treats the tumour. A stereotactic biopsy (image-guided needle sampling performed under MRI guidance) is generally reserved for tumours where resection is judged to be unsafe, and provides tissue for diagnosis alone. Modern neuropathological diagnosis requires comprehensive molecular testing — including IDH mutational status, 1p/19q codeletion, ATRX, TERT, and CDKN2A/B — in addition to microscopic examination.¹

Functional MRI (fMRI) and Diffusion Tensor Imaging (DTI)

These specialised MRI techniques map the relationship between the tumour and critical brain functions such as speech and movement. They are not required in every case, but are helpful — and are routinely used — where resection is considered risky, or where the tumour lies close to functionally important (eloquent) areas of the brain, to help plan the safest possible operation.

Intraoperative neurophysiological monitoring and awake craniotomy

For tumours located in or near critical functional brain areas (eloquent cortex), the operation can be tailored to protect those functions. Movement (motor) pathways can increasingly be mapped with the patient asleep under general anaesthetic, using intraoperative motor mapping — an emerging alternative to awake surgery for motor testing, though many centres still perform motor mapping awake. Mapping of language, however, still requires an awake craniotomy, in which the patient is woken for part of the operation so that speech can be tested in real time while the tumour is removed. These techniques help the surgeon remove as much tumour as safely possible while preserving function.⁴

Should a Low-Grade Glioma be Treated — and When?

This is one of the most nuanced and actively debated questions in neuro-oncology. Not all patients require immediate active treatment after surgery. Key factors considered include:

Patient age — younger patients are generally considered at lower risk of early progression
Extent of surgical resection — greater resection is consistently associated with longer survival and reduced risk of malignant transformation; this is now endorsed by international guidelines as the primary surgical goal4
Tumour size — larger tumours, particularly those exceeding 6 cm, carry a higher risk of early progression
IDH mutation status — IDH-wildtype (non-mutated) tumours require prompt treatment given their poor prognosis
1p/19q codeletion — its presence favourably influences treatment response
Neurological symptoms — tumours causing significant neurological deficits require treatment
Patient wishes and quality of life — anxiety about an untreated tumour, occupational requirements, and personal preference are all valid treatment considerations

Depending on these factors, the options after surgery range from careful observation with regular MRI monitoring, through targeted therapy with vorasidenib for suitable IDH-mutant grade 2 tumours, to radiotherapy combined with chemotherapy for higher-risk disease.

All patients should be discussed at a dedicated multidisciplinary neuro-oncology meeting, involving a neurosurgeon, neuro-oncologist, radiation oncologist, neuropathologist, and neuroradiologist, to determine the optimal timing and type of treatment for each individual.4

How are Low-Grade Gliomas Treated?

Surgery — Maximal Safe Resection

Surgery is both the method of obtaining tissue for diagnosis and the first active treatment for the large majority of patients. The goal of surgery is maximal safe resection — removing as much of the tumour as possible whilst preserving neurological function. A larger extent of resection (ideally gross total resection) is consistently associated with longer progression-free survival, longer overall survival, and a reduced risk of malignant transformation.⁴Because low-grade gliomas do not enhance with contrast, a gross total resection is defined by removal of all the abnormal signal on the T2/FLAIR MRI sequences, rather than by loss of contrast enhancement as in a high-grade tumour. Modern surgical techniques — including intraoperative MRI, cortical and subcortical mapping (performed awake for language, and increasingly with the patient asleep under general anaesthetic for motor pathways), fluorescent dye-guided resection, and intraoperative ultrasound — allow surgeons to safely maximise resection in ways not previously possible. Surgery should be performed by a neurosurgeon experienced in low-grade glioma surgery at a centre with appropriate operative expertise. For tumours in inaccessible or highly eloquent locations where resection carries unacceptable risk, stereotactic biopsy alone may be appropriate — but the treating team and patient should understand this results in a more limited initial treatment effect and does not address tumour burden. A further limitation of biopsy is that it samples only a small part of the tumour: because gliomas are not uniform throughout, a biopsy can under-sample the lesion and miss an area of higher grade or different molecular features, so the resulting pathology may be incomplete or, occasionally, inaccurate.

Vorasidenib — Targeted Therapy

Vorasidenib is a preferred initial adjuvant therapy option following surgery where there is no or minimal residual disease, or when upfront radiotherapy and chemotherapy is not preferred. This is the first oral targeted therapy specifically developed for IDH-mutant low-grade gliomas. It inhibits the mutant IDH1 and IDH2 enzymes that drive tumour development. A phase III randomised trial (INDIGO trial) reported significantly improved progression-free survival compared to placebo, representing the first targeted treatment advance in this disease.⁶ This agent became available on the Pharmaceutical Benefits Scheme (PBS) in Australia on 1 August 2026 for patients with a grade 2 astrocytoma or oligodendroglioma with an IDH mutation who have not been treated with chemotherapy or radiotherapy.

Radiotherapy

Radiotherapy — using carefully targeted beams of high-energy radiation to damage tumour cells — is a well-established and effective treatment for low-grade gliomas. It is generally not administered immediately after surgery for all patients, but is recommended when the patient has features placing them at higher risk of early progression (“high-risk” features), including:⁷

Age ≥ 40 years
Astrocytoma (rather than oligodendroglioma) subtype
Incomplete surgical resection
Larger tumour size (≥ 6 cm)
Tumour crossing the midline
Presence of a pre-operative neurological deficit
IDH-wildtype status (a more recently recognised, biologically-based risk factor)

The standard dose of radiotherapy for low-grade gliomas is 45–54 Gy delivered in daily fractions over approximately 5–6 weeks. Higher doses have not been shown to improve outcomes and carry greater risk of long-term cognitive effects.⁴

Chemotherapy — PCV and Temozolomide

Chemotherapy given in combination with radiotherapy has been demonstrated in landmark randomised clinical trials to substantially improve survival in high-risk low-grade gliomas. There are two primary chemotherapy regimens:

PCV (Procarbazine, CCNU [Lomustine], and Vincristine) — The RTOG 9802 phase III randomised trial, published in the New England Journal of Medicine in 2016, demonstrated that radiotherapy followed by six cycles of PCV chemotherapy significantly improved both progression-free survival and overall survival compared to radiotherapy alone, with a striking improvement in median overall survival from 7.8 years (radiotherapy alone) to 13.3 years (radiotherapy plus PCV).⁸ This benefit was most pronounced in patients with IDH-mutant tumours and even more so in those with 1p/19q codeletion (oligodendrogliomas). Radiotherapy with adjuvant PCV is now considered the standard of care for high-risk patients with IDH-mutant gliomas. PCV can be difficult to tolerate — approximately half of patients experience significant haematological toxicity — but its survival benefit is substantial.

Temozolomide (TMZ) — A simpler oral chemotherapy agent with a more favourable side-effect profile than PCV, temozolomide is widely used in neuro-oncology. The EORTC 22033-26033 phase III trial found that temozolomide alone did not demonstrate superior progression-free survival compared to radiotherapy alone in high-risk low-grade gliomas.⁹ However, the recently reported ECOG-ACRIN E3F05 phase III randomised trial (presented at the Society for Neuro-Oncology Annual Meeting, 2024) demonstrated for the first time that the addition of temozolomide to radiotherapy significantly improved long-term survival in grade 2 glioma patients, providing the first randomised evidence supporting combined radiation and temozolomide in this setting.¹⁰ Whether PCV or temozolomide is the preferred chemotherapy partner with radiotherapy is an area of ongoing investigation.

What Happens After Treatment — Surveillance and Recurrence

Following surgery and adjuvant treatment, regular MRI monitoring is mandatory for all patients with low-grade gliomas, as the majority will eventually progress. The frequency of MRI depends on the treatment received and individual risk factors, but is typically every 3–6 months in the first years following active treatment, extending to every 6–12 months for stable disease.⁴ Tumour recurrence and malignant transformation — the evolution of the tumour to a higher grade — are the central challenges of low-grade glioma management. When recurrence occurs, treatment options include repeat surgery, radiotherapy (if not previously administered), and chemotherapy (PCV or temozolomide). Clinical trial participation at the time of recurrence is encouraged wherever possible. Patients and their families should be aware that low-grade glioma management is a long-term process, typically measured in years to decades, requiring ongoing specialist follow-up. The treating team will guide decisions about each step of management as the clinical situation evolves.

References

Louis DN, Perry A, Wesseling P, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021;23(8):1231-1251. doi:10.1093/neuonc/noab106
van den Bent MJ, Geurts M, French PJ, et al. Primary brain tumours in adults. Lancet. 2023;402(10412):1564-1579. doi:10.1016/S0140-6736(23)01054-1
Cancer Genome Atlas Research Network; Brat DJ, Verhaak RGW, Aldape KD, et al. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med. 2015;372(26):2481-2498. doi:10.1056/NEJMoa1402121
Weller M, van den Bent M, Preusser M, et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat Rev Clin Oncol. 2021;18(3):170-186. doi:10.1038/s41571-020-00447-z
Broen MPG, Smits M, Wijnenga MMJ, et al. The T2-FLAIR mismatch sign as an imaging marker for non-enhancing IDH-mutant, 1p/19q-intact lower-grade glioma: a validation study. Neuro Oncol. 2018;20(10):1393-1399. doi:10.1093/neuonc/noy048
Mellinghoff IK, van den Bent MJ, Blumenthal DT, et al. Vorasidenib in IDH1- or IDH2-mutant low-grade glioma. N Engl J Med. 2023;389(7):589-601. doi:10.1056/NEJMoa2304194
Pignatti F, van den Bent M, Curran D, et al. Prognostic factors for survival in adult patients with cerebral low-grade glioma. J Clin Oncol. 2002;20(8):2076-2084. doi:10.1200/JCO.2002.08.121
Buckner JC, Shaw EG, Pugh SL, et al. Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. N Engl J Med. 2016;374(14):1344-1355. doi:10.1056/NEJMoa1500925
Baumert BG, Hegi ME, van den Bent MJ, et al. Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study. Lancet Oncol. 2016;17(11):1521-1532. doi:10.1016/S1470-2045(16)30313-8
Schiff D, O’Neill A, Brown PD, et al. Radiation therapy plus temozolomide versus radiation therapy alone in high-risk low-grade glioma (ECOG-ACRIN E3F05): a phase III randomized trial. Presented at: Society for Neuro-Oncology Annual Meeting; November 2024.

Helpful links



Low-Grade Gliomas — patient information sheet PDF · prepared by Mr Jeremy Russell

Download PDF

Content on this page is for education and information only and is not a substitute for advice from your doctor. Medically reviewed by Mr Jeremy Russell.