Review articlePaediatric brain tumours: A review of radiotherapy, state of the art and challenges for the future regarding protontherapy and carbontherapyTumeurs cérébrales pédiatriques : revue de la littérature en radiothérapie, état de l’art et défis pour l’avenir en ce qui concerne la protonthérapie et la carbonethérapie
Introduction
Brain tumours are the most frequent paediatric solid tumours in children. In most cases, treatment includes surgery and radiotherapy with or without chemotherapy. Paediatric brain tumours acutely raise the question of treatments long-term tolerance. According to paediatric brain tumour natural history, the treatment is either addressing the general spreading of the disease or the local invasion and often both. Whenever the local control is the upfront challenge for the cure rate, the role of surgery and radiation therapy is important. The main drawback of radiation therapy is its acute and late toxicity that are particularly serious for central nervous system in childhood. Intelligence quotient impairment and other functional loss are well-documented. The challenge is therefore to improve the local control with less toxicity by identifying very accurately the target and avoiding irradiation of normal tissues outside the target.
Although surgery could be improved by postoperative assessment and sophisticate imaging, more improvement could come from altered radiotherapy technics as particle therapy. Actually, the better dose localization of particle therapy opens the possibility to increase target dose and to decrease organs at risk dose in the same time. Even more, in case of really very radioresistant tumours, heavy ions could be used with the same possibility of organs at risk sparing. Actually, protontherapy is a highly conformal treatment, able to reduce the absorbed dose to the normal brain parenchyma, the optic pathways, hypothalamus and sensorial organs.
However, one should consider also the risk of undue relapses while changing from larger integrated dose with photons to more localized dose of protons, due to uncertainties of the microscopic extend of the disease [1]. Similarly, uncertainties are remaining about the relative biological efficiency of particle therapy especially for children normal brain, and for tumours.
Thus, a complex figure of multiple parameters is existing in the domain of paediatric tumours including pattern of spreading and relapse, targets nature and location, tumour sensitivity, age of the patients, side-effects risk, that are influencing the possibilities of improvement by the use of particle therapy.
In France, presently, there is only one high-energy protontherapy center (ICPO, Orsay) able to treat such tumours [2]. The other French protontherapy center (Impact/Médicyc, Nice) is getting upgraded to access high energy, and there are several other projects. There is a need to determine how many regional referral centres, equipped with such technique, are necessary in France. An analysis of all indications for adults and children must be performed. This prompted the radiotherapy committee of the French society of childhood cancers (Société française de lutte contre les cancers et les leucémies de l’enfant et de l’adolescent [SFCE]), to join the France Hadron consortium to define the indications of particle therapy for paediatric brain tumours. The France Hadron consortium includes existing particle therapy centres (ICPO in Orsay and Impact/Medicyc in Nice), as well as projects (centre Étoile in Lyon, Archade in Caen, Périclès in Toulouse).
The present paper reviews the toxicity and impairment data regarding paediatric central nervous system tumours, then details, for each type of paediatric brain tumours, the present challenges, the contribution of radiotherapy as a treatment component and the possibilities to improve it including by the use of particle therapy, and, how to assess this by evidence-based medicine approaches.
Cognitive dysfunction and endocrinopathy are the most frequent side effects of brain radiation therapy. Depending on tumour location; auditive and visual impairment are also frequent. Vasculopathy with stroke and second cancers are much less frequent.
Additionally, in case of craniospinal irradiation, decreased bone growth is constant, risks on lung and heart function do exist [3], [4], [5].
Moreover, the use of anticancer agent is a cause of second cancer.
Section snippets
Methods
Prior to the literature research, an expert group identified the potential indications for hadrontherapy (proton and carbon) in terms of tumour location and/or histology according to basic principle. These principles were: radioresistant unresectable tumours surrounded by organ at risk, with mainly local–regional spreading for patients lacking heavy comorbidities.
The Medline database and Cochrane Library (from January 1966 to March 2014) were used to perform the search. The query equation was
Gliomas
Glioma, according to their pathological grade and anatomic location, are of different level of life-threatening seriousness which is described thereafter (Table 1).
Low-grade gliomas are the most commonly diagnosed brain tumour in children and the most common cause of child brain irradiation. The overall survival rate being rather good, the main concern is the treatment related late toxicity, which justifies the search for alternatives to the use of radiotherapy.
High-grade glioma are rare in
Discussion
Paediatric radiotherapy is often considered as a two-edged weapon. On one edge, a necessary and efficient treatment for children's solid tumour, particularly brain tumours, on the other edge, a source of mild to severe late effects: cognitive, endocrinal, auditory and visual. In the everyday practice of paediatric radiation oncology, the question of referral to a protontherapy centre is frequent but resources are scarce and no national guidelines exist for paediatric brain tumour. This prompted
Conclusion
In France, 600 children every year receive a radiotherapy and brain tumours radiation therapy is the most frequent indication. To this, we can add the adolescents and young adults population. The number of indications for protons in a curative setting in paediatric and adolescents and young adults with brain tumours is 410 per year. Therefore, the need for protontherapy for such internationally acknowledged development, added to the other recognized and reimbursed indications (other paediatric
Disclosure of interest
The authors declare that they have no competing interest.
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SFCE : Société française de lutte contre les cancers et les leucémies de l’enfant et de l’adolescent (French society of childhood cancers).