In principle, proton therapy (PT) offers a substantial clinical advantage over photon-based therapy. This is due to the depth-dose characteristics of protons, which can be exploited to achieve dose reduction in normal tissues proximal and distal to the target volume.
In paediatric oncology, use of PT is often advocate to reduce toxicity, second cancer, and improve quality of live in patients with a long live expectancy.
Retrospective studies and monocentric phase II trials, especially for brain tumours, show encouraging results in term of efficacy and side effects.
Recent technical improvements allow wider use of PT but limitations persist apart to the high cost.
With the increase in the number of patients treated, concerns have arisen after description of unexpected post-therapeutic radiological changes and brainstem necrosis occurring after irradiation for CNS tumours. Risk factors as young age or combined chemotherapy are well known. Since adopting strict dose constraints to brainstem, the risk of symptomatic injury has decreased without affecting tumour control.
Radiobiological uncertainties could also play a role. In clinical practice, RBE (Relative Biological Effectiveness) of protons is assumed to have a constant value of 1.1. However, RBE can increase at the distal edge of the beam. RBE increase with depth reflect an increase of LET (Linear Energy Transfer). Some data suggest that radiologic modifications are located in area with a high LET. Development of tools to integrate LET or RBE variations in treatment planning is ongoing. Some TPS (treatment planning system) already propose LET assessment. In the future, biological treatment optimization will be possible.
Due to protons physical proprieties, dose distribution in PT is more sensitive to uncertainties from intra- and inter-fraction variation in anatomy. PT requires regular imaging control and re-plan in case of anatomic modification. Limitation of organ movement related to breathing or filling is recommended but it is not always feasible in young patients by lack of collaboration. Robust optimization taking into account breathing with 4D CT and simulation of density variation is an alternative. With use of PBS (Pencil Beam Scanning), dose repainting is an option to minimize the impact of intra-fraction organ motion.
Presence of metallic device close to the target volume can affect the accuracy of the treatment plan due to artefacts in the planning CT scan and approximation of the dose calculation method. In that case, use of common metal artefact reduction (MAR) algorithms or dual energy CT is recommended to improve imaging quality of planning CT, facilitate delineation and reduce calculation uncertainties. Integration of implants composition in dose calculation is also required. Ballistics avoiding beam pass through metallic material are preferred. In some cases, multidisciplinary discussion at diagnosis can overcome this limitation by offering pre-operative irradiation, use of non-metallic implants or the postponement of spinal fixation.
Combination with other radiation techniques can also help to reduce uncertainties in dose distribution while keeping the ballistic advantage of protons.
In conclusion, PT is a promising tool in paediatric treatment but uncertainties in dose distribution may limit its potential advantages. PT is complementary to other highly precise radiation techniques. Treatment planning and plan evaluation require special considerations compared to photon.