Glioblastoma

Under the 2021 WHO classification, glioblastoma is an IDH-wildtype diffuse astrocytic tumour of adults, CNS WHO grade 4. The diagnosis can be made either on histology (microvascular proliferation or necrosis) or, in a tumour that lacks these features, on molecular grounds: TERT promoter mutation, EGFR amplification, or gain of chromosome 7 with loss of chromosome 10^[1]. IDH-mutant grade 4 tumours are now called astrocytoma, IDH-mutant, grade 4, and have a better prognosis. Methylation of the MGMT promoter predicts benefit from temozolomide^[2].

Patients, usually in their sixth or seventh decade, present over weeks with progressive focal deficits, seizures, headache from raised intracranial pressure, or cognitive and personality changes, depending on tumour location. The rapid tempo of symptoms is typical.

MRI shows an irregular, rim-enhancing mass with central necrosis and surrounding T2/FLAIR hyperintensity, which contains both oedema and infiltrating tumour. Crossing of the corpus callosum (“butterfly glioma”) and multifocality occur. The differential includes metastasis, lymphoma (homogeneous enhancement, restricted diffusion), abscess (restricted diffusion in the cavity) and tumefactive demyelination. Perfusion imaging and spectroscopy help. For tumours near eloquent cortex or tracts, functional MRI and diffusion tensor tractography are used for planning, and corticosteroids reduce oedema before surgery. Steroids should be avoided when lymphoma is suspected until tissue is obtained.

Retrospective series show that a greater extent of resection of the enhancing tumour is associated with longer survival. In 416 patients, resection of 98% or more of the enhancing volume was associated with a significant survival advantage^[3], and a later volumetric analysis found a benefit beginning at around 78% resection, increasing stepwise toward complete resection^[4]. In a randomised trial, 5-aminolevulinic acid (5-ALA) fluorescence guidance raised the rate of complete resection of enhancing tumour from about a third to about two thirds of patients and improved six-month progression-free survival compared with white-light surgery^[5]. New neurological deficits worsen survival, so the goal is maximal resection without new deficit.

The Stupp regimen of radiotherapy (60 Gy in 30 fractions) with concurrent daily temozolomide, followed by six cycles of adjuvant temozolomide, increased median survival from 12.1 to 14.6 months and two-year survival from about 10% to 27%^[6]; the benefit is concentrated in patients with MGMT-methylated tumours^[2]. Adding tumour-treating fields to maintenance temozolomide further prolonged median survival in a randomised trial^[7]. Elderly or frail patients receive shorter-course radiotherapy, temozolomide alone (for MGMT-methylated tumours), or best supportive care.

• Plan the corridor with navigation and tractography; for eloquent tumours, use awake language mapping or asleep motor mapping with subcortical stimulation.
• Give oral 5-ALA before induction and resect fluorescent tissue where it is safe to do so.
• Begin with devascularisation at the margins when feasible, and work circumferentially along the tumour–brain interface.
• Intraoperative MRI or ultrasound can identify residual tumour before closure.
• Biopsy (stereotactic or open) is preferred for deep, bilateral or diffuse tumours where resection is not safe.

Despite optimal therapy, recurrence is nearly universal, usually at the resection margin. Age, performance status, extent of resection and MGMT status are the main prognostic factors. Repeat surgery can benefit selected patients at recurrence, especially those with good performance status and a resectable lesion.