Case Reports:
Recurrent extraneural sonic hedgehog medulloblastoma exhibiting sustained response to vismodegib and temozolomide monotherapies and inter-metastatic molecular heterogeneity at progression
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Abstract
Gregorio J. Petrirena1, Julien Masliah-Planchon2,3, Quentin Sala4, Bertrand Pourroy5, Didier Frappaz6, Emeline Tabouret1,7, Thomas Graillon8, Jean-Claude Gentet9, Olivier Delattre2,3, Olivier Chinot1,7 and Laetitia Padovani10
1Service de Neuro-Oncologie, Hôpital La Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France
2Unité de Génétique Somatique, Département de Génétique Oncologique, Institut Curie, Paris, France
3INSERM_U830, Institut Curie, Paris, France
4Service de Médecine Nucléaire, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Marseille, France
5Unité Oncopharma, Service Pharmacie, Hôpital La Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France
6Service de Neuro-Oncologie Pédiatrique et Adulte, Centre Léon Bérard, Lyon, France
7Aix-Marseille Université, Marseille, France
8Service de Neurochirurgie, Hôpital La Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France
9Service d’Oncologie et Hématologie Pédiatrique, Hôpital La Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France
10Service de Radiothérapie, Hôpital La Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France
Correspondence to:
Gregorio J. Petrirena, email: [email protected]
Keywords: sonic hedgehog medulloblastoma; vismodegib; temozolomide; smoothened mutation; PIK3CA mutation
Received: June 03, 2017 Accepted: November 01, 2017 Published: January 03, 2018
ABSTRACT
Background: Response to targeting and non-targeting agents is variable and molecular information remains poorly described in patients with recurrent sonic-hedgehog-driven medulloblastoma (SHH-MB).
Materials and Methods: Clinical and PET/CT findings during treatment with successive hedgehog antagonists and temozolomide monotherapies are described in a heavily pre-treated patient with recurrent extraneural metastases from PTCH1 mutated/ wild type smoothened (SMO) CNS SHH-MB. Molecular tests were prospectively performed in tissue from two extraneural sites at progression.
Results: Sustained clinical/metabolic response was obtained to vismodegib. At progression, itraconazole was ineffective, but salvage temozolomide treatment results in a response similar to vismodegib. At further progression, acquired SMO and PIK3CA mutations were identified in bone (G477L and H1047A, respectively) and epidural (L412P and H1065L, respectively) metastases. No response was observed with subsequent sonidegib treatment.
Conclusions: This is the first clinical report of recurrent extraneural PTCH1 mutated SHH-MB exhibiting: 1) a sustained response to vismodegib and temozolomide, and 2) inter-metastatic molecular heterogeneity and acquired SMO-G477L, SMO-L412P, and PIK3CA-H1065L mutations at progression, highlighting the need for a multitarget treatment approach.
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PII: 23699