Case Report: Proton beam therapy – friend or foe for patients with IDH-mutated WHO grade 2 and 3 gliomas?

Background Proton beam therapy is increasingly implemented for lower-grade gliomas worldwide, aiming to reduce radiation exposure to healthy tissue and lower treatment related toxicity. However, robust clinical evidence of the benefit of radiotherapy delivered with protons compared to photons is lacking. Importantly, although proton therapy offers potential benefits compared to photon radiotherapy, it is still ionizing radiation and can be associated with severe complications. Emerging concerns include a possible increase of radiotherapy-induced contrast-enhancing lesions. Case presentation A healthy woman in her mid-forties underwent a subtotal resection for an IDH- mutated oligodendroglioma CNS WHO grade 2. She was randomized to proton therapy in the PRO-GLIO trial and received a dose of 54 Gray (Gy) relative biological effectiveness (RBE), followed by chemotherapy. Ten months after completion of radiotherapy, she reported rapid visual deterioration ultimately resulting in blindness. She also developed substantial cognitive deficits, pituitary and hypothalamic failure, and a general decline. MRI showed considerable, progressive radionecrosis in large parts of the irradiated brain. Tragically, the patient passed away 22 months after completing proton therapy. Conclusion This case highlights that although proton beam therapy is considered safe and potentially encumbered with fewer side effects than photon radiotherapy, serious complications may occur. Careful consideration of timing and execution of adjuvant therapy for lower-grade gliomas is essential. Randomized controlled trials are necessary to disclose if proton beam therapy is beneficial or not in lower-grade gliomas.