Treatment of Adamantinomatous Craniopharyngioma with Somatic CTNNB1 Mutation When Standard Therapy Has Failed
This protocol addresses patients with the adamantinomatous subtype of craniopharyngioma (ACP) carrying a somatic CTNNB1 gene mutation or demonstrating nuclear beta-catenin immunopositivity, without BRAF V600E mutation, in whom standard treatment has not achieved adequate disease control.
Molecular Markers
The adamantinomatous subtype is confirmed by anti-beta-catenin immunostaining demonstrating a nuclear pattern. A somatic CTNNB1 mutation — and exceptionally an APC mutation — is the molecular hallmark of ACP, identifying the patients for whom this treatment pathway applies.
Treatment Approach (Partial Overview)
When standard therapy has not controlled this tumour, a dedicated multidisciplinary tumour board evaluates whether targeted therapy is appropriate. In eligible patients, MEK inhibitor therapy is one class of intervention that may be considered. The complete set of options, eligibility criteria, and clinical decision algorithm is available in the full protocol.
Treatment goal: Initial tumour shrinkage and prolonged stabilization on MRI.
References
DOI: 10.1016/j.ando.2024.07.002
- Anti-beta-catenin immunostaining is recommended to confirm the adamantinomatous subtype of craniopharyngioma (nuclear staining) (strong).
- The presence of a CTNNB1 mutation (and exceptionally of APC mutation) points to ACP.
- If standard treatment fails, targeted therapies (MEK or VEGF inhibitors, biotherapies) for adamantinomatous craniopharyngiomas should be discussed by a dedicated tumor multidisciplinary board (weak).
- Trametinib has shown promising results.
- Binimetinib, 45 mg b.i.d. resulted in initial tumor shrinkage over 8 months and prolonged stabilization in a young woman with multi-recurrent ACP.
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