Prospective Evaluation of Neurocognitive Integrity After Proton Therapy for Brain Tumor

In the brain, late radiotoxicities typically manifest as cognitive dysfunction, leukoencephalopathy, brain atrophy, brain tissue necrosis, cerebrovascular complications, endocrinopathies, and/or secondary malignant neoplasms.

Radiation-induced hippocampal injury, in particular, significantly contributes to cognitive impairment, while broader central nervous system effects arise through multiple mechanisms, including vascular injury, neuronal depletion, chronic inflammation, demyelination, and tissue necrosis.

The severity of cognitive dysfunction depends on multiple factors, including the location and the volume of the tumor, the total radiation dose administered, the fractionation regimen, and the individual susceptibility of the patient, as well as comorbidities (e.g., diabetes, etc.) and concomitant drugs.

The distinct physical characteristics of proton therapy, such as a reduced entrance dose, an eliminated exit dose, and a Bragg peak, provide clear dosimetric advantages over conventional photon treatments. Pencil-beam scanning further improves on earlier passive scattering approaches by delivering modulated proton beamlets for superior target conformality and reduced neutron scatter, thereby limiting low- and intermediate- dose exposure to cranial organs at risk (OARs) while preserving adequate dose coverage within the target volume.

From a radiobiological standpoint, these properties suggest that proton therapy may present a more favorable risk-benefit balance compared to photon-based modalities, particularly for long-term clinical outcomes. It achieves a drastic reduction in the integral dose, offering substantial benefit in decreasing radiation-induced second malignancies, making it mandatory for children when available.