title: Paediatric brain tumours: A review of radiotherapy, state of the art and challenges for the future regarding protontherapy and carbontherapy.
abstract: OBJECTIVE
  Brain tumours are the most frequent solid tumours in children and the most frequent radiotherapy indications in paediatrics, with frequent late effects: cognitive, osseous, visual, auditory and hormonal. A better protection of healthy tissues by improved beam ballistics, with particle therapy, is expected to decrease significantly late effects without decreasing local control and survival. This article reviews the scientific literature to advocate indications of protontherapy and carbon ion therapy for childhood central nervous system cancer, and estimate the expected therapeutic benefits.
  
  
  METHODS
  A systematic review was performed on paediatric brain tumour treatments using Medline (from 1966 to March of 2014). To be included, clinical trials had to meet the following criteria: age of patients 18 years or younger, treated with radiation, and report of survival. Studies were also selected according to the evidence level. A secondary search of cited references found other studies about cognitive functions, quality of life, the comparison of photon and proton dosimetry showing potential dose escalation and/or sparing of organs at risk with protontherapy; and studies on dosimetric and technical issues related to protontherapy.
  
  
  RESULTS
  A total of 7051 primary references published were retrieved, among which 40 clinical studies and 60 papers about quality of life, dose distribution and dosimetry were analysed, as well as the ongoing clinical trials. These papers have been summarized and reported in a specific document made available to the participants of a final 1-day workshop. Tumours of the meningeal envelop and bony cranial structures were excluded from the analysis. Protontherapy allows outstanding ballistics to target the tumour area, while substantially decreasing radiation dose to the normal tissues. There are many indications of protontherapy for paediatric brain tumours in curative intent, either for localized treatment of ependymomas, germ-cell tumours, craniopharyngiomas, low-grade gliomas; or panventricular irradiation of pure non-secreting germinoma; or craniospinal irradiation of medulloblastomas and metastatic pure germinomas. Carbon ion therapy is just emerging and may be studied for highly aggressive and radioresistant tumours, as an initial treatment for diffuse brainstem gliomas, and for relapse of high-grade gliomas.
  
  
  CONCLUSIONS
  Both protontherapy and carbon ion therapy are promising for paediatric brain tumours. The benefit of decreasing late effects without altering survival has been described for most paediatric brain tumours with protontherapy and is currently assessed in ongoing clinical trials with up-to-date proton devices. Unfortunately, in 2015, only a minority of paediatric patients in France can receive protontherapy due to the lack of equipment.
authors.affiliation: Université Paul-Sabatier, Toulouse, France; Institut Claudius-Regaud, institut universitaire du cancer de Toulouse (IUCT)-Oncopole, radiation oncology, 1, avenue Irene-Joliot-Curie, 31059 Toulouse, France; Périclès-France-Hadron, Toulouse, France. Electronic address: laprie.anne@iuct-oncopole.fr.
authors.forename: A
authors.initials: A
authors.lastname: Laprie
authors.affiliation: GCS-Étoile-France-Hadron, Lyon, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Institut Curie Paris Orsay (ICPO)-France-Hadron, Orsay, France.
authors.forename: C
authors.initials: C
authors.lastname: Alapetite
authors.affiliation: GCS-Étoile-France-Hadron, Lyon, France; Centre Léon-Bérard, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Carrie
authors.affiliation: Institut Curie Paris Orsay (ICPO)-France-Hadron, Orsay, France; Université Paris Sud, Orsay, France; Archade-France-Hadron, Caen, France; Centre François-Baclesse, Caen, France; Gustave-Roussy, Villejuif, France.
authors.forename: J-L
authors.initials: JL
authors.lastname: Habrand
authors.affiliation: Institut Curie Paris Orsay (ICPO)-France-Hadron, Orsay, France; Impact-France-Hadron, Nice, France.
authors.forename: S
authors.initials: S
authors.lastname: Bolle
authors.affiliation: Centre Antoine-Lacassagne, Nice, France; CHU de Bordeaux, Bordeaux, France.
authors.forename: P-Y
authors.initials: PY
authors.lastname: Bondiau
authors.affiliation: Institut Claudius-Regaud, institut universitaire du cancer de Toulouse (IUCT)-Oncopole, radiation oncology, 1, avenue Irene-Joliot-Curie, 31059 Toulouse, France; Périclès-France-Hadron, Toulouse, France.
authors.forename: A
authors.initials: A
authors.lastname: Ducassou
authors.affiliation: Hôpital des Enfants, Toulouse, France.
authors.forename: A
authors.initials: A
authors.lastname: Huchet
authors.affiliation: Périclès-France-Hadron, Toulouse, France; Université Grenoble Alpes, Grenoble, France.
authors.forename: A-I
authors.initials: AI
authors.lastname: Bertozzi
authors.affiliation: Université Grenoble Alpes, Grenoble, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Perel
authors.affiliation: Université Paul-Sabatier, Toulouse, France; Institut Claudius-Regaud, institut universitaire du cancer de Toulouse (IUCT)-Oncopole, radiation oncology, 1, avenue Irene-Joliot-Curie, 31059 Toulouse, France; Périclès-France-Hadron, Toulouse, France.
authors.forename: É
authors.initials: É
authors.lastname: Moyal
authors.affiliation: GCS-Étoile-France-Hadron, Lyon, France; CHU de Grenoble, Grenoble, France.
authors.forename: J
authors.initials: J
authors.lastname: Balosso
mesh_terms: D001932:Brain Neoplasms / Q000532:radiotherapy*; D002648:Child; D005544:Forecasting; D063193:Heavy Ion Radiotherapy; D006801:Humans; D017410:Practice Guidelines as Topic; D061766:Proton Therapy; D011522:Protons
chemical_list: D011522:Protons
keywords: Carbontherapy; Craniopharyngioma; Craniopharyngiome; Craniospinal irradiation; Ependymoma; Germ-cell tumours; Irradiation crâniospinale; Medulloblastoma; Médulloblastome; Paediatric brain tumour; Protontherapy; Protonthérapie; Thérapie par ions carbone; Tumeur germinale; Tumeurs cérébrales pédiatriques; Épendymome