Improvement Opportunities in the Multimodal Treatment of Pediatric Brain Tumors

Resumen

The treatment of pediatric CNS tumors remains one of the major challenges in modern pediatric oncology. The general aim of this study is to improve the management of these patients, on a multilevel approach: At an institutional/local, national and international/European level. Three research projects were carried out: In Research Project #1, a monocentric review of all pediatric patients with medulloblastoma treated between 2003 and 2016 at Hospital Niño Jesús, Madrid, was performed. While the global outcome of the 58 included patients was similar to the outcome observed in European population-based studies (5-year OS: 59%), several measures were proposed to improve the identified weak areas. These measures include implementing a quality assurance system, promoting the inclusion in international clinical trials, establishing a central pathology review, accelerating the translation of the new molecular knowledge into daily practice, and implementing a neurocognitive and QOL evaluation program. Moreover, a set of 27 quality indicators to evaluate the management of these patients was developed. In Research Project #2, all pediatric patients with non-medulloblastoma CNS embryonal tumors treated in eight major oncology centers in Spain between 2005 and 2014 were reviewed. The 43 included patients presented a dismal outcome (3-year OS: 35%), especially when compared to patients included in clinical trials. Establishing a common national strategy, implementing referral circuits and collaboration networks, and incorporating new molecular knowledge into routine clinical practice were proposed as accessible measures that can improve the outcome of these patients. Additionally, a retrospective molecular analysis (methylation profiling) of tumor samples of this patient cohort was started. In Research Project #3, the radiotherapy quality assurance (RTQA) systems in past and current clinical trials protocols for pediatric CNS tumors were analyzed. Several initiatives to implement RTQA, both at national and international levels, are being developed across Europe. Furthermore, a survey about the practices of RTQA in pediatric CNS tumors across 21 European countries was performed. As a result, five key measures were proposed: Creating a European RTQA guideline for pediatric CNS tumors, improving the collaboration between pediatric oncologists and radiation oncologists, building a European central storage system for RT data, implementing international RTQA platforms, and promoting European referral networks to reduce inequality. Overall, this thesis shows that there are several aspects to be improved in the management of pediatric patients with CNS tumors, and proposes a set of pragmatic measures with a three-level approach: local, national and international. Hopefully, this work will contribute to the global improvement of survival and quality of life of children and adolescents with CNS tumors.