PROTON BEAM THERAPY FOR PEDIATRIC CNS TUMORS: AN OVERVIEW OF ONGOING TRIALS

PROTON BEAM THERAPY FOR PEDIATRIC CNS TUMORS: AN OVERVIEW OF ONGOING TRIALS Aims: Radiotherapy (RT) represents a fundamental approach in the multimodal management of pediatric central nervous system (CNS) tumors and modern technologies are improving the dose-sparing of developing normal tissues with the aim to reduce the risk of late toxicities and secondary malignancies.Proton Beam Therapy (PBT) could lead to achieve these results due to the physical characteristics of protons.In this work we provide an overview of the ongoing trials which are evaluating the role of PBT in this setting. Methods: On 6th May 2019 we searched on clinicaltrials.gov website the following keywords: “Pediatric CNS tumors” and “Proton beam therapy”.We specifically included studies enrolling only pediatric patients and we excluded studies in suspended,terminated,withdrawn or unknown status. Results: Our search provided nine trials.Among them, three were in recruiting status and six were active but not recruiting.Centers in the United States were the major investigators.Two studies had Results: the NCT00105560 trial confirmed that PBT for medulloblastoma had similar survival outcomes compared to conventional RT, with acceptable toxicity; the NCT00602667 study – which is evaluating a risk-adapted approach to reduce radiation exposure in young children with medulloblastoma – suspended the option of consolidative PBT in intermediate-risk patients and continued focal photon-RT. The NCT01180881 and the NCT02559752 trials are assessing neurobehavioral functioning and neurocognitive performance after PBT, respectively.Information on patients’ quality of life after PBT (also for pediatric non-CNS tumors) are being collected in the NCT01115777 study.The NCT03281889 trial is studying bone spine-sparing PBT in pediatric craniospinal radiation with the aim to reduce the growth-decline.Acute and late toxicities of PBT craniospinal irradiation, as well as survival outcomes and treatment efficiency, are also being evaluating in the NCT01063114 trial.Similarly, the NCT01067196 trial is studying late effects and survival outcomes of PBT for CNS tumors.Finally, the NCT03696355 trial is assessing the antitumor activity of GDC-0084 in patients with diffuse pontine/midline gliomas and its combined effects with PBT/RT. Conclusions: Preliminary results suggest that PBT may represent an alternative to photon-treatments for pediatric CNS tumors, especially for medulloblastoma.Confirms from ongoing prospective studies are necessary to clearly define PBT effectiveness and safety.