Stereotactic radiosurgery for brain metastases from malignant melanoma and the impact of hemorrhagic metastases |
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Authors: | Kristine Bauer-Nilsen Daniel M. Trifiletti Ajay Chatrath Henry Ruiz-Garcia Eduardo Marchan Jennifer Peterson Byron C. May Jason P. Sheehan |
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Affiliation: | 1.Pediatric and Adolescent Drug Development, Children and Young People’s Unit,The Royal Marsden NHS Foundation Trust – Paediatric Offices,Sutton,UK;2.Division of Clinical Studies and Cancer Therapeutics,The Institute of Cancer Research,Sutton,UK;3.Department of Pediatric and Adolescent Oncology, Gustave Roussy, UMR 8203, CNRS,Univ. Paris-Sud,Villejuif,France;4.Clinical Trials Unit, Pediatric Oncology Department,Hospital Infantil Universitario Ni?o Jesús,Madrid,Spain;5.Department of Pediatric, Adolescents and Young Adults Oncology,Institut Curie,Paris,France;6.Department of Pediatric Oncology,Vall d’Hebron Hospital,Barcelona,Spain;7.Department of Pediatric Clinical Trials and Department of Pediatric Neuro-Oncology,Institut Hématologique et d’Oncologie Pédiatrique,Lyon,France;8.Pediatric Oncology Unit,Fondazione IRCCS Istituto Nazionale dei Tumori,Milan,Italy;9.Department of Pediatric Oncology,Birmingham Children’s Hospital,Birmingham,UK;10.Department of Pediatric Oncology,Notthingham Children’s Hospital,Nottingham,UK;11.Université Paris Descartes,Paris,France;12.Pediatric Oncology Unit,Great Ormond Street Hospital for Children NHS Foundation Trust,London,UK;13.Department of Clinical Research, Gustave Roussy,Université Paris-Sud,Villejuif,France |
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Abstract: | ![]() Central nervous system (CNS) tumors are a leading cause of death in pediatric oncology. New drugs are desperately needed to improve survival. We evaluated the outcome of children and adolescents with CNS tumors participating in phase I trials within the Innovative Therapies for Children with Cancer (ITCC) consortium. Patients with solid tumors aged?18 years at enrollment in their first dose-finding trial between 2000 and 2014 at eight ITCC centers were included retrospectively. Survival was evaluated using univariate/multivariate analyses. Overall, 114 patients were included (109 evaluable for efficacy). Median age was 10.2 years (range 1.0–17.9). Main diagnoses included: medulloblastoma/primitive neuroectodermal tumors (32.5%) and high-grade gliomas (23.7%). Complete/partial responses (CR/PR) were reported in 7.3% patients and stable disease (SD) in 23.9%. Performance status of 90–100%, school/work attendance, normal ALT/AST and CR/PR/SD correlated with better overall survival (OS) in the univariate analysis. No variables assessable at screening/enrollment were associated with OS in the multivariate analysis. Five patients (4.5%) were discontinued from study due to toxicity. No toxic deaths occurred. Median OS was 11.9 months with CR/PR, 14.5 months with SD and 3.7 months with progressive disease (p?0.001). The enrollment of children and adolescents with CNS tumors in phase I trials is feasible, safe and offers potential benefit for the patients. Sustained disease stabilization has a promising role as a marker of anti-tumor activity in children with CNS tumors participating in phase I trials. |
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