Alexandre Roux1,2,3, Johan Pallud1,2,3, Raphaël Saffroy4, Myriam Edjlali-Goujon5, Marie-Anne Debily6,7, Nathalie Boddaert2,8, Marc Sanson9,10, Stéphanie Puget2,11, Steven Knafo12, Clovis Adam13, Thierry Faillot14, Dominique Cazals-Hatem15, Emmanuel Mandonnet16,17, Marc Polivka2,3,18, Georges Dorfmüller19, Aurélie Dauta20, Mathilde Desplanques21, Albane Gareton2, Mélanie Pages2,3,18, Arnault Tauziede-Espariat2,3, Jacques Grill6,22, Franck Bourdeaut2,23, François Doz2,23, Frédéric Dhermain24, Karima Mokhtari8,25, Fabrice Chretien1, Dominique Figarella-Branger26, Pascale Varlet2,3. 1. Department of Neurosurgery, University Hospital Group (GHU) Paris-Sainte-Anne Hospital, Paris, France. 2. Paris Descartes University, Sorbonne Paris Cité, Paris, France. 3. Inserm Unit 1266, Imaging Biomarkers of Brain Disorders, Institute of Psychiatry and Neurosciences of Paris, Paris, France. 4. Department of Biochemistry, Paul-Brousse Hospital, Villejuif, France. 5. Department of Neuroradiology, Sainte-Anne Hospital, Paris, France. 6. Inserm Unit 981, Biomarkers and New Therapeutic Targets in Oncology Team, Genomics and Oncogenesis of Brain Tumors, Paris-Sud University, Paris-Saclay University, Villejuif, France. 7. Evry University, Paris-Saclay University, Evry cedex, France. 8. Department of Neuroradiology, Necker Enfants-Malades Hospital, Paris, France. 9. Brain and Spine Institute (ICM), Experimental Neuro-Oncology Department, Inserm U1127, Sorbonne University, Paris, France. 10. Department of Neurology 2, Mazarin Unit, Pitié-Salpêtrière Hospital, Paris, France. 11. Department of Neurosurgery, Necker Enfants-Malades Hospital, Paris, France. 12. Department of Neurosurgery, Bicêtre Hospital, Paris-Sud University, Kremlin-Bicêtre, France. 13. Department of Pathology, Bicêtre Hospital, Paris-Sud University, Kremlin-Bicêtre, France. 14. Department of Neurosurgery, Beaujon Hospital, Clichy, France. 15. Department of Pathology, Beaujon Hospital, Clichy, France. 16. Department of Neurosurgery, Lariboisière Hospital, Paris, France. 17. Paris 7 University, Paris, France. 18. Department of Pathology, Lariboisière Hospital, Paris, France. 19. Department of Pediatric Neurosurgery, Rothschild Foundation Hospital, Paris, France. 20. Department of Neurosurgery, Henri-Mordor Hospital, Créteil, France. 21. Department of Neuropathology, GHU Paris-Sainte-Anne Hospital, Paris, France. 22. Department of Pediatric Oncology, Gustave-Roussy University Hospital, Paris-Sud University, Paris-Saclay University, Villejuif, France. 23. SIREDO Oncology Center (Care, Innovation and Research for Children and AYA with Cancer), Institut Curie, Paris, France. 24. Department of Radiotherapy, Gustave Roussy University Hospital, Villejuif, France. 25. Department of Neuropathology, Pitié-Salpêtrière Hospital, Paris, France. 26. Department of Pathology and Neuropathology, Timone Hospital, Marseille, France.
Abstract
BACKGROUND: Considering that pediatric high-grade gliomas (HGGs) are biologically distinct from their adult counterparts, the objective of this study was to define the landscape of HGGs in adolescents and young adults (AYAs). METHODS: We performed a multicentric retrospective study of 112 AYAs from adult and pediatric Ile-de-France neurosurgical units, treated between 1998 and 2013 to analyze their clinicoradiological and histomolecular profiles. The inclusion criteria were age between 15 and 25 years, histopathological HGG diagnosis, available clinical data, and preoperative and follow-up MRI. MRI and tumoral samples were centrally reviewed. Immunohistochemistry and complementary molecular techniques such as targeted/next-generation sequencing, whole exome sequencing, and DNA-methylation analyses were performed to achieve an integrated diagnosis according to the 2016 World Health Organization (WHO) classification. RESULTS: Based on 80 documented AYA patients, HGGs constitute heterogeneous clinicopathological and molecular groups, with a predominant representation of pediatric subtypes (histone H3-mutants, 40%) but also adult subtypes (isocitrate dehydrogenase [IDH] mutants, 28%) characterized by the rarity of oligodendrogliomas, IDH mutants, and 1p/19q codeletion and the relative high frequency of "rare adult IDH mutations" (20%). H3G34-mutants (14%) represent the most specific subgroup in AYAs. In the H3K27-mutant subgroup, non-brainstem diffuse midline gliomas are more frequent (66.7%) than diffuse intrinsic pontine gliomas (23.8%), contrary to what is observed in children. We found that WHO grade has no prognostic value, but molecular subgrouping has major prognostic importance. CONCLUSIONS: HGGs in AYAs could benefit from a specific classification, driven by molecular subtyping rather than age group. Collaborative efforts are needed from pediatric and adult neuro-oncology teams to improve the management of HGGs in AYAs.
BACKGROUND: Considering that pediatric high-grade gliomas (HGGs) are biologically distinct from their adult counterparts, the objective of this study was to define the landscape of HGGs in adolescents and young adults (AYAs). METHODS: We performed a multicentric retrospective study of 112 AYAs from adult and pediatric Ile-de-France neurosurgical units, treated between 1998 and 2013 to analyze their clinicoradiological and histomolecular profiles. The inclusion criteria were age between 15 and 25 years, histopathological HGG diagnosis, available clinical data, and preoperative and follow-up MRI. MRI and tumoral samples were centrally reviewed. Immunohistochemistry and complementary molecular techniques such as targeted/next-generation sequencing, whole exome sequencing, and DNA-methylation analyses were performed to achieve an integrated diagnosis according to the 2016 World Health Organization (WHO) classification. RESULTS: Based on 80 documented AYA patients, HGGs constitute heterogeneous clinicopathological and molecular groups, with a predominant representation of pediatric subtypes (histone H3-mutants, 40%) but also adult subtypes (isocitrate dehydrogenase [IDH] mutants, 28%) characterized by the rarity of oligodendrogliomas, IDH mutants, and 1p/19q codeletion and the relative high frequency of "rare adult IDH mutations" (20%). H3G34-mutants (14%) represent the most specific subgroup in AYAs. In the H3K27-mutant subgroup, non-brainstem diffuse midline gliomas are more frequent (66.7%) than diffuse intrinsic pontine gliomas (23.8%), contrary to what is observed in children. We found that WHO grade has no prognostic value, but molecular subgrouping has major prognostic importance. CONCLUSIONS: HGGs in AYAs could benefit from a specific classification, driven by molecular subtyping rather than age group. Collaborative efforts are needed from pediatric and adult neuro-oncology teams to improve the management of HGGs in AYAs.
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