Does Proton Therapy Have a Future in CNS Tumors?

OPINION STATEMENT: Proton therapy is characterized by certain physical properties leading to a reduction in integral dose. As proton therapy becomes more widely available, the ongoing discussion on the real indications for proton therapy becomes more important. In the present article, data on proton therapy for tumors of the central nervous system (CNS) is summarized and discussed in view of modern photon treatments. Still today, no randomized controlled trials are available confirming any clinical benefit of protons in CNS tumors. For certain skull base lesions, such as chordomas and chondrosarcomas, dose escalation is possible with protons thus patients should be referred to a proton center if readily available. For vestibular schwannoma, at present, proton data are inferior to advanced photons. For glioma patients, early data is present for low-grade gliomas, presenting comparable results to photons; dose escalation studies for high-grade gliomas have led to significant side effects, thus strategies of dose-escalation need to rethought. For skull base meningiomas, data from stereotactic series and IMRT present excellent local control with minimal side effects, thus any improvement with protons might only be marginal. The largest benefit is considered in pediatric CNS tumors, due to the intricate radiation sensitivity of children's normal tissue, as well as the potential of long-term survivorship. Long-term data is still lacking, and even recent analyses do not all lead to a clear reduction in side effects with improvement of outcome; furthermore, clinical data seem to be comparable. However, based on the preclinical evidence, proton therapy should be evaluated in every pediatric patient. Protons most likely have a benefit in terms of reduction of long-term side effects, such as neurocognitive sequelae or secondary malignancies; moreover, dose escalation can be performed in radio-resistant histologies. Clinical data with long-term follow-up is still warranted to prove any superiority to advanced photons in CNS tumors. If available, protons should be evaluated for chordoma or chondrosarcoma of the skull base and pediatric tumors. However, many factors are important for excellent oncology care, and no time delay or inferior oncological care should be accepted for the sake of protons only.