Trials and papersGlioma & glioblastoma

Young adults with a grade 2 IDH-mutant glioma who have had surgery can now take a daily tablet that slows or reverses tumour growth and defers radiotherapy and chemotherapy, both of which carry long-term cognitive costs, by years. It confirms that the IDH mutation is a driver that can be targeted, not just a marker. Whether it improves survival or cognition over the long term, and whether it helps in higher-grade or previously treated tumours, is unknown.

This is the evidence behind a national approval, and it is 19 patients in a single arm. The survival figure is genuinely higher than historical expectation in recurrent glioblastoma, and the biopsy findings support the immune mechanism. It is not a randomised comparison, and the imaging pattern means the usual response criteria cannot be used, which makes an uncontrolled result harder rather than easier to interpret.

This is what legitimate repurposing looks like: a registered dose-finding trial that reports its toxicities. It says nothing yet about whether mebendazole helps glioblastoma.

The clearest randomised refutation in the field. Phase 1 data had looked encouraging, the delivery problem was solved by surgical access, and the killing mechanism was a well-understood chemotherapy released in place. None of it translated. Any claim that oncolytic virotherapy works in glioma has to be read against this trial.

With the Nordic trial, NOA-08 made MGMT testing the way to choose between temozolomide alone and radiotherapy alone for older patients with glioblastoma who are not offered combined treatment.

This paper connected the cancer stem cell idea to a clinical problem, the near-universal recurrence of glioblastoma after radiotherapy, and gave a mechanism and a drug target. It is part of the rationale for combining radiotherapy with DNA damage response inhibitors now in trials.

Patients with newly diagnosed glioblastoma who are fit and under about 70 receive six weeks of radiotherapy with daily temozolomide followed by six monthly cycles of temozolomide; this is still the backbone of treatment two decades later. Testing MGMT methylation identifies who benefits most and guides decisions in older patients. Median survival with the regimen remains only around 15-20 months, and no drug since has clearly improved on it, which is why glioblastoma is a priority for new approaches.

This paper extended the cancer stem cell model to brain tumours and set up the later finding that these cells resist radiotherapy. It is the basis for treatment strategies aimed at the cells that regrow glioblastoma after surgery and chemoradiation.