Upfront Radiation Therapy Increases Severe Neurotoxicity Risk in Patients With Oligodendrogliomas

Oligodendrogliomas are rare malignant brain tumors with median survivals exceeding fifteen years after treatment with chemoradiation therapy. Long lifespans increase risk for adverse treatment effects. We retrospectively reviewed outcomes after early upfront radiation therapy (RT) or RT deferred until disease progression to determine whether toxicity and survivals were different.

At our institution, patients with WHO 2 oligodendrogliomas are offered observation until progression and WHO 3 tumors are offered chemotherapy followed by RT. We retrospectively reviewed long term outcomes of 80 consecutive patients with isocitrate dehydrogenase (IDH) mutant and 1p19q codeleted oligodendrogliomas treated between 2005 and 2021. We defined severe toxicity as stroke, dementia, and cerebral radiation necrosis.

After maximal safe resection, 33/80 patients were treated with upfront RT followed by chemotherapy, 30/80 received upfront chemotherapy with radiation deferred until progression, and 17/80 patients received no therapy. Almost half (n=15/33, 45%) treated with early RT suffered radiation necrosis (n=3), stroke (n=2), or disabling dementia (n=9), compared with two patients (n=2/30, 6.7%) suffering radiation necrosis without disability who did not receive radiation until disease progression. There was no difference in progression-free or overall survival, median follow-up after WHO 3 diagnosis or number of deaths between the groups. The group treated with upfront RT had longer post-radiation follow-up duration.

Upfront RT was associated with a substantially higher rate of severe delayed toxicity, including radiation necrosis, stroke, and disabling dementia, without an apparent survival benefit. These findings support deferring RT until disease progression to reduce long-term treatment-related morbidity.