Contents lists available at ScienceDirect Cancer Treatment Reviews journal homepage: www.elsevier.com/locate/ctrv Anti-Tumour Treatment Current status of proton therapy outcome for paediatric cancers of the central nervous system – Analysis of the published literature Myxuan Huynh a , Loredana Gabriela Marcu a,b , Eileen Giles a , Michala Short a , Donna Matthews a , Eva Bezak a,c, ⁎ a Cancer Research Institute and School of Health Sciences, University of South Australia, Adelaide, SA 5001, Australia b Faculty of Science, University of Oradea, Oradea 410087, Romania c School of Physical Sciences, University of Adelaide, North Terrace, Adelaide, South Australia 5005, Australia ARTICLE INFO Keywords: Proton therapy Paediatric cancers CNS Adverse events ABSTRACT Introduction: The most common solid tumours that develop in children are cancers of the central nervous system. Due to the increased rate of survival over the past decades, greater focus has been placed on the minimisation of long term side effects. In childhood cancer survivors, over 60% report one or more radiation-related late toxi- cities while half of these adverse events are graded as life-threatening or severe. Proton therapy enables high conformity with the planning target volume and a reduction in dose to areas beyond the target. Owing to the unique nature of dose delivery with proton therapy a reduction of low doses to normal tissues is achievable, and is believed to allow for a decrease in long-term treatment-related side effects. This paper aims to review the published literature around the effectiveness of proton therapy for the treatment of paediatric cancers of the central nervous system, with a focus on treatment outcomes and treatment-related toxicities. Methods: A search strategy utilising the Medline database was created with the intent of including all articles reporting on proton therapy, paediatric cancers, CNS tumours and treatment outcomes. The final search strategy included the following limitations: limited to humans, English, published from 2000 onwards. The final article count total was 74. Results and conclusions: Proton therapy for the treatment of paediatric cancers of the central nervous system was found to provide survival and tumour control outcomes comparable to photon therapy. Reduced incidence of severe acute and late toxicities was also reported with the use of proton therapy. This includes reduced severity of endocrine, neurological, IQ and QoL deficits. Currently, extensive follow-up of proton patient populations still needs to be made to determine incidences of late-onset toxicities and secondary malignancies. Current evidence surrounding proton therapy use in paediatric patients supports its effectiveness and potential benefits in redu- cing the incidence of severe toxicities in later life. Introduction The most common solid tumours that develop in children originate in the central nervous system (CNS) [1]. Paediatric CNS cancers differ from adult CNS tumours in origin, classification, histology distribution, incidence, and anatomical location [2]. Below the age of fifteen, CNS tumours represent 20% of all cancers, and are commonly located below the tentorium in the posterior fossa. In comparison to adults, an in- creased incidence of medulloblastoma tumours and reduced incidence of meningioma tumours are present in children [2]. CNS tumours also share distinctive characteristics including an undetectable premalignant or in-situ stage, ability for low-grade tumours to infiltrate large brain regions, and ability for tumour spread to distant sites via the neuroaxis [3]. Regardless of histological classi- fication of CNS tumours, prognostic outcomes are largely dependent on the anatomical location of the tumour, dictated by tumour growth on proximal critical structures and the general resectability of the primary neoplasm [3]. Treatment of CNS tumours often comes with adverse events which can be aggravated in young patients. Current therapeutic strategies for CNS tumours include a combination of surgery, chemotherapy and radiotherapy, as shown in the section below. https://doi.org/10.1016/j.ctrv.2018.10.003 Received 18 August 2018; Received in revised form 5 October 2018; Accepted 6 October 2018 ⁎ Corresponding author at: Cancer Research Institute and School of Health Sciences, University of South Australia, Adelaide 5001, Australia. E-mail address: Eva.Bezak@unisa.edu.au (E. Bezak). Cancer Treatment Reviews 70 (2018) 272–288 0305-7372/ © 2018 Elsevier Ltd. All rights reserved. T