Proton therapy (PT) has been administered for many years to a number of cancers, including brain tumours. Due to their remarkable physical properties, delivering their radiation to a very precise brain volume with no exit dose, protons are particularly appropriate for these tumours. The decrease of the brain integral dose may translate with a diminution of neuro-cognitive toxicity and increase of quality of life, particularly so in children. The brain tumour patient’s access to PT will be substantially increased in the future, with many new facilities being planned or currently constructed in Europe, Asia and the United States. Although approximately 150’000 patients have been treated with PT, no level I evidence has been demonstrated for this treatment. As such, it is this necessary to generate high-quality data and some new prospective trials will include protons or will be activated to compare photons to protons in a randomized design. PT comes however with an additional cost factor that may contribute to the ever-growing health’s expenditure allocated to cancer management. These additional costs and financial toxicity will have to be analysed in the light of a more conformal radiation delivery, non-target brain irradiation and lack of potential for dose escalation when compared to photons. The latter is due to the radiosensitivity of organs at risk in vicinity of the brain tumour, that photons cannot spare optimally. Consequentially, radiation-induced toxicities and tumour recurrences, which are cost-intensive, may decrease with PT resulting in an optimized photon/proton financial ratio in the end. Advances in knowledge: This review details the indication of brain tumors for proton therapy and give a list of the open prospective trials for these challenging tumors.

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Background: Long-term treatment-related toxicity may substantially impact wellbeing, quality of life (QoL), and health of children/adolescents with brain tumors (CBTs). Strategies to reduce toxicity include pencil beam scanning (PBS) proton therapy (PT). This study aims to report clinical outcomes and QoL in PBS-treated CBTs. Procedure: We retrospectively reviewed 221 PBS-treated CBTs aged <18 years. Overall-free (OS), disease-free (DFS), and late-toxicity-free survivals (TFS), local control (LC) and distant (DC) brain/spinal control were calculated using Kaplan-Meier estimates. Prospective QoL reports from 206 patients (proxies only ≤4 years old [yo], proxies and patients ≥5 yo) were descriptively analyzed. Median follow-up was 51 months (range, 4-222). Results: Median age at diagnosis was 3.1 years (range, 0.3-17.7). The main histologies were ependymoma (n = 88; 39.8%), glioma (n = 37; 16.7%), craniopharyngioma (n = 22; 10.0%), atypical teratoid/rhabdoid tumor (ATRT) (n = 21; 9.5%) and medulloblastoma (n = 15; 6.8%). One hundred sixty (72.4%) patients received chemotherapy. Median PT dose was 54 Gy(relative biological effectiveness) (range, 18.0-64.8). The 5-year OS,