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.

Objective: To assess the radiation-induced optic neuropathy (RION) prevalence, following high dose pencil beam scanning proton therapy (PBSPT) to skull base and head and neck (H&N) tumours Methods: Between 1999 and 2014, 216 adult patients, median age 47 years (range, 18–77), were treated with PBS PT for skull base or H&N malignancies, delivering ≥45 GyRBE to the optic nerve(s) (ON) and/or optic chiasma (OC). The median administered dose to the planning target volume was 74.0 GyRBE (range, 54.0–77.4). The median follow-up was 5.3 years (range, 0.8–15.9). Results: RION was observed in 14 (6.5%) patients at a median time of 13.2 months (range, 4.8–42.6) following PBSPT. Most (92.9%) of RION were symptomatic. Most affected patients (11/14; 79%) developed unilateral toxicity. Grade 4, 3, 2 and 1 toxicity was observed in 10, 2, 1 and 1 patients, respectively. On univariate analyses, age (<70 vs ≥70 years; p < 0.0001), hypertension (p = 0.0007) and tumour abutting the optic apparatus (p = 0.012) were associated with RION. OC’s V60 GyRBE was of border line significance (p = 0.06). None of the other evaluated OC–ON dose/volume metrics (Dmax, Dmean, V40-60) were significantly associated with this complication. Conclusion: These data suggest that high-dose PBS PT for skull base and H&N tumours is associated with a low prevalence of RION. Caution should be however exercised when treating elderly/hypertensive patients with tumours abutting the optic apparatus. Advances in knowledge: This is the first study reporting the risk of developing RION following proton therapy with PBS technique, demonstrating the safety of this treatment.

The aim of this study was to assess the clinical outcome, including QoL, of patients with intracranial meningiomas WHO grade 1–3 who were treated with Pencil Beam Scanning Proton Therapy (PBS PT) between 1997 and 2022. Two hundred patients (median age 50.4 years, 70% WHO grade 1) were analyzed. Acute and late side effects were classified according to CTCAE version 5.0. Time to event data were calculated. QoL was assessed descriptively by the EORTC-QLQ-C30 and BN20 questionnaires. With a median follow-up of 65 months (range: 3.8–260.8 months) the 5 year OS was 95.7% and 81.8% for WHO grade 1 and grade 2/3, respectively (p < 0.001). Twenty (10%) local failures were observed. Failures occurred significantly (p < 0.001) more frequent in WHO grade 2 or 3 meningioma (WHO grade 1: n = 7, WHO grade 2/3: n = 13), in patients with multiple meningiomas (p = 0.005), in male patients (p = 0.005), and when PT was initiated not as upfront therapy (p = 0.011). There were no high-grade toxicities in the majority (n = 176; 88%) of patients. QoL was assessed for 83 (41.5%) patients and for those patients PT did not impacted QoL negatively during the follow-up. In summary, we observed very few local recurrences of meningiomas after PBS PT, a stable QoL, and a low rate of high-grade toxicity.