No abstract

e21509 Background: Participation of children with advanced solid cancers in phase I trials raises ethical and logistic dilemmas. Life-expectancy beyond 8-12 weeks is a common inclusion criterion, but it can be difficult to gauge. This multicentric European study assessed the mortality and survival rates in pediatric phase I trials. Methods: Retrospective study of patients aged < 18 years with solid tumors enrolled in phase I trials in ITCC centres between 2015-2017. Outcome variables were described and prognostic factors analysed. Results: 256 patients across 12 centres in 5 countries were eligible. Median age 11.8 years (range, 0.5-17.9). Female:Male ratio 1:1.9. Tumor location: central nervous system (CNS) 66% vs extra-CNS 34%. Main diagnoses: 22% soft tissue sarcomas, 13% high grade gliomas, 11% osteosarcomas. Most frequent therapy: single targeted agent (63%). Ten cases (4%) were not evaluable for response and 128 (50%) had progressive disease at first evaluation. Best responses were complete in 12 cases (5%), partial in 29 (11%) and stable disease in 77 (30%). Median follow-up 7 months (range, 0.5-42.4). Median Time On Study (TOS) 2.1 months (range, 0.2-38.1). The 30 and 90-day mortality on trial were 3% (8/256) and 21% (54/256), respectively. The 90-day survival (95%CI) for patients with CNS vs extra-CNS tumors was 88% (78-93) vs 76% (68-82), respectively. One-year Overall Survival (95%CI) for the whole sample was 40% (33-46). No toxic deaths on trial were reported. Twenty-five cases (10%) survived ≥365 days on trial. Median TOS 21.5 months (range, 12.3-38.1). Compared to patients who died within 365 days from Cycle1-Day1, those on trial ≥365 days had lower rates of metastatic disease (74% vs 28%, respectively, p < 0.001), higher objective response rates (13% vs 44%, respectively, p < 0.001) and higher disease stabilization (27% vs 56%, respectively, p < 0.001). Conclusions: Currently few patients die within the first cycle of treatment. However a fifth of all patients died within 3 months from trial initiation. Patients with CNS tumors have comparable survival rates to those with extra-CNS and should not be excluded from phase I trials solely because of their diagnosis. The survival rates beyond one year remain modest.

Los autores declaran no tener ningún tipo de interés económico o comercial. ReSuMenObjetivo: Con esta búsqueda sistemática pretendíamos en un principio contrastar los diferentes tratamientos ortopodológicos utilizados en el pie plano flexible (PPF). Material y métodos: Se ha realizado una revisión de la literatura científica para identificar los posibles estudios de los diferentes tratamientos para el pie plano flexible. Se han consultado los principales buscadores y bases de datos biomédicas: Medline-pubmed, Enfispo, Scopus y Cochrane Library®. El periodo de búsqueda estuvo comprendido entre febrero-junio de 2011. Resultados: En nuestra búsqueda hallamos 150 resúmenes de artículos con las palabras clave seleccionadas. 106 artículos de los anteriormente mencionados fueron excluidos tras leerlos por no cumplir los criterios de selección del estudio. Por lo tanto, obtuvimos 44 potencialmente relevantes. De estos, 4 eran estudios sobre tratamientos conservadores para el PPF, 17 sobre tratamientos quirúrgicos, 22 eran análisis descriptivos de la materia y 1 revisión sistemática. Conclusiones: Con esta búsqueda, destacamos la falta de estudios con tratamientos ortoprotésicos y conservadores en general, existiendo, por el contrario, una amplia bibliografía sobre estudios en multitud de técnicas quirúrgicas aplicadas al PPF. Por lo cual, en investigaciones futuras se deberían obtener métodos de clasificación del PPF válidos y fiables que faciliten el estudio y nos aporten medidas de resultados adecuadamente valoradas para la intervención que se está llevando a cabo. La investigación debería dirigirse en el futuro a realizar ensayos clínicos que incluyan a mayor número de pacientes, que comparen diferentes combinaciones y algoritmos de formas de tratamiento conservadores, para analizar su coste-efectividad a medio-largo plazo. Palabras clave: pie plano flexible; soporte plantar; ortesis plantares; tratamiento conservador; tratamiento quirúrgico.

No abstract

Objectives: Neuroblastoma is the most common extracranial tumour in children, and prognosis for refractory and relapsed disease is still poor. Early-phase clinical trials play a pivotal role in the development of novel drugs. Ensuring adequate recruitment is crucial. The primary aim was to determine the rate of participation trials for children with refractory/relapsed neuroblastoma in two of the largest drug development European institutions.Methods: Data from patients diagnosed with refractory/relapsed neuroblastoma between January 2012 and December 2018 at the two institutions were collected and analysed.Results: Overall, 48 patients were included. A total of 31 (65%) refractory/relapsed cases were enrolled in early-phase trials. The main reasons for not participating in clinical trials included not fulfilling eligibility criteria prior to consent (12/17, 70%) and screening failure (2/17, 12%). Median time on trial was 4.3 months (range 0.6-13.4). Most common cause for trial discontinuation was disease progression (67.7%).Median overall survival was longer in refractory (28 months, 95% CI: 20.9-40.2) than in relapsed patients (14 months, 95% CI: 8.1-20.1) (p = .034). Conclusions:Although two thirds of children with refractory/relapsed neuroblastoma were enrolled in early-phase trials, recruitment rates can still be improved. The main cause for not participating on trials was not fulfilling eligibility criteria prior to consent, mainly due to performance status and short life expectancy. This study highlights the hurdles to access to innovative therapies for children with relapsed/refractory neuroblastomas, and identifies key areas of development to improve recruitment to earlyphase trials.