Stephanie Puget1,2,3, Kevin Beccaria4,5, Thomas Blauwblomme4,5, Thomas Roujeau4,5, Syril James4,5, Jacques Grill6, Michel Zerah4,5, Pascale Varlet7, Christian Sainte-Rose4,5. 1. Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, 149 rue de Sèvres, 75015, Paris, France. stephanie.puget@gmail.com. 2. Sorbonne Paris Cité, Université Paris Descartes, Paris, France. stephanie.puget@gmail.com. 3. UMR CNRS 8203 "Vectorologie et Thérapeutiques Anticancéreuses", Département de Cancérologie de l'Enfant et de l'Adolescent, Institut de Cancérologie Gustave Roussy, 114 rue Edouard Vaillant, 94805, Villejuif cedex, France. stephanie.puget@gmail.com. 4. Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, 149 rue de Sèvres, 75015, Paris, France. 5. Sorbonne Paris Cité, Université Paris Descartes, Paris, France. 6. Department of Pediatric and Adolescent Oncology and CNRS UMR 8203 "Vectorology and Anticancer Therapeutics", Gustave Roussy Cancer Institute, Universite Paris Sud, 114 rue Edouard Vaillant, 94805, Villejuif, France. 7. Department of Neuropathology, Sainte-Anne Hospital, 1 rue Cabanis, 75014, Paris, France.
Abstract
PURPOSE: Diffuse intrinsic pontine glioma (DIPG) is the most severe pediatric solid tumor, with no significant improvement in the past 50 years. Possible reasons for failure to make therapeutic progress include poor understanding of the underlying molecular biology due to lack of tumor material. METHODS: We performed a prospective analysis of children with typical appearance of DIPG who had a stereotactic biopsy in our unit since 2002. Technical approach, complications, histopathological results, and samples processing are exposed. The literature on this subject is discussed. RESULTS: Reviewing our own 130 cases of DIPG biopsies and previous published data, these procedures appear to have a diagnostic yield and morbidity rates similar to those reported for other brain locations (3.9 % of transient morbidity in our series). In addition, the quality and the quantity of the material obtained allow to (1) confirm the diagnosis, (2) reveal that WHO grading was useless to predict outcome, and (3) perform an extended molecular screen, including biomarkers study and the development of preclinical models. Recent studies reveal that DIPG may comprise more than one biological entity and a unique oncogenesis involving mutations never described in other types of cancers, i.e., histones H3 K27M and activin receptor ACVR1. CONCLUSION: Stereotactic biopsies of DIPG can be considered as a safe procedure in well-trained neurosurgical teams and could be incorporated in protocols. It is a unique opportunity to integrate DIPG biopsies in clinical practice and use the biology at diagnosis to drive the introduction of innovative targeted therapies, in combination with radiotherapy.
PURPOSE: Diffuse intrinsic pontine glioma (DIPG) is the most severe pediatric solid tumor, with no significant improvement in the past 50 years. Possible reasons for failure to make therapeutic progress include poor understanding of the underlying molecular biology due to lack of tumor material. METHODS: We performed a prospective analysis of children with typical appearance of DIPG who had a stereotactic biopsy in our unit since 2002. Technical approach, complications, histopathological results, and samples processing are exposed. The literature on this subject is discussed. RESULTS: Reviewing our own 130 cases of DIPG biopsies and previous published data, these procedures appear to have a diagnostic yield and morbidity rates similar to those reported for other brain locations (3.9 % of transient morbidity in our series). In addition, the quality and the quantity of the material obtained allow to (1) confirm the diagnosis, (2) reveal that WHO grading was useless to predict outcome, and (3) perform an extended molecular screen, including biomarkers study and the development of preclinical models. Recent studies reveal that DIPG may comprise more than one biological entity and a unique oncogenesis involving mutations never described in other types of cancers, i.e., histones H3 K27M and activin receptor ACVR1. CONCLUSION: Stereotactic biopsies of DIPG can be considered as a safe procedure in well-trained neurosurgical teams and could be incorporated in protocols. It is a unique opportunity to integrate DIPG biopsies in clinical practice and use the biology at diagnosis to drive the introduction of innovative targeted therapies, in combination with radiotherapy.
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