Top Line: What are the long term outcomes with RT alone or TMZ alone for high risk, low grade glioma?
The Study: Back in the early 2000s, there were questions over the timing of radiation for low grade glioma, there were concerns about late radiation adverse effects, and temozolomide was all the rage. EORTC 22033 was a phase 3 trial designed to see if temozolomide would be as effective as radiation but less neurocognitive adverse effects in patients with low grade glioma at high risk of progression based on clinical factors. It included 478 patients with high risk, WHO grade 2 glioma who were randomized to 50.4 Gy in 28 fractions or 12 cycles of temozolomide. The trial showed no difference in PFS or OS between arms, and it also failed to ever demonstrate that TMZ reduced any neurocognitive effects relative to RT. However, we now manage these tumors based on molecular classification. So, in this long term followup, the authors reclassified 73% of tumors based on the 2021 WHO molecular criteria. Overall, there was still no difference in median OS or PFS. For IDH-mut, non-codeleted astrocytomas (51%), there was no difference in OS (RT 6.6 years v TMZ 6.7 years). For IDH-mut, codeleted oligodendrogliomas (31%), there was no difference in OS (RT 12.9 v TMZ 14.9 years). For the small subset of IDH-wt astrocytomas (18%, now classified as glioblastomas), survival actually favored TMZ (4.7 v 2.5 years).
TBL: Though we now treat most of these patients with some combination of chemo and radiation, there are no long term differences in survival outcomes between radiation and TMZ in situations where a patient may only be eligible for single modality therapy. | Baumert, J Clin Oncol 2026
The Study: Back in the early 2000s, there were questions over the timing of radiation for low grade glioma, there were concerns about late radiation adverse effects, and temozolomide was all the rage. EORTC 22033 was a phase 3 trial designed to see if temozolomide would be as effective as radiation but less neurocognitive adverse effects in patients with low grade glioma at high risk of progression based on clinical factors. It included 478 patients with high risk, WHO grade 2 glioma who were randomized to 50.4 Gy in 28 fractions or 12 cycles of temozolomide. The trial showed no difference in PFS or OS between arms, and it also failed to ever demonstrate that TMZ reduced any neurocognitive effects relative to RT. However, we now manage these tumors based on molecular classification. So, in this long term followup, the authors reclassified 73% of tumors based on the 2021 WHO molecular criteria. Overall, there was still no difference in median OS or PFS. For IDH-mut, non-codeleted astrocytomas (51%), there was no difference in OS (RT 6.6 years v TMZ 6.7 years). For IDH-mut, codeleted oligodendrogliomas (31%), there was no difference in OS (RT 12.9 v TMZ 14.9 years). For the small subset of IDH-wt astrocytomas (18%, now classified as glioblastomas), survival actually favored TMZ (4.7 v 2.5 years).
TBL: Though we now treat most of these patients with some combination of chemo and radiation, there are no long term differences in survival outcomes between radiation and TMZ in situations where a patient may only be eligible for single modality therapy. | Baumert, J Clin Oncol 2026