Successful treatment of a TSC2-mutant glioblastoma with everolimus

• Published in: BMJ case reports Vol. 12; no. 5; p. e227734
• Main Authors: Zureick, Andrew H, McFadden, Kathryn A, Mody, Rajen, Koschmann, Carl
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 31.05.2019; BMJ Publishing Group
• Series: Case Report
• Subjects: Adolescent; Brain cancer; Brain Neoplasms - complications; Brain Neoplasms - diagnosis; Brain Neoplasms - diagnostic imaging; Brain Neoplasms - therapy; Cancer therapies; Case reports; Chemotherapy; Combined Modality Therapy; Diagnosis, Differential; Diplopia - etiology; Everolimus - therapeutic use; Glioblastoma - complications; Glioblastoma - diagnosis; Glioblastoma - diagnostic imaging; Glioblastoma - therapy; Histology; Humans; Immunosuppressive Agents - therapeutic use; Inhibitor drugs; Li-Fraumeni Syndrome; Male; Medical prognosis; Mutation; Novel Treatment (New Drug/Intervention; Established Drug/Procedure in New Situation); Oncology; Parietal Lobe; Pathology; Patients; Pediatrics; Precision Medicine; Radiation therapy; Stains & staining; Targeted cancer therapy; Temporal Lobe; Tuberous Sclerosis Complex 2 Protein - genetics; paediatric oncology; cancer intervention; CNS cancer; neuro-oncology
• ISSN: 1757-790X; 1757-790X
• DOI: 10.1136/bcr-2018-227734

A 14-year-old boy with familial Li-Fraumeni syndrome presented with diplopia. Brain MRI revealed a right temporoparietal rim-enhancing mass. Following surgical resection and diagnosis of a gigantocellular-type glioblastoma multiforme (GBM), his family wished to avoid cytotoxic chemotherapy given the amplified risk of secondary malignancy. As such, we performed whole exome and transcriptome sequencing, which revealed germline TP53 and somatic TSC2 mutations. On completion of adjuvant radiotherapy, he was started on maintenance therapy with everolimus per recommendations from our multi-institutional brain tumour precision medicine tumour board. He has achieved a complete remission with resolution of visual symptoms and remains on everolimus therapy with concurrent electromagnetic field therapy, now 33 months from diagnosis. Our data highlight the benefit of precision medicine in children with GBM and offer insight into a targetable pathway that may be involved in similar cases.