Treatment with BRAF/MEK-inhibitors in mutant BRAF-V600E papillary craniopharyngioma

Abstract

Craniopharyngiomas (CPs) are rare brain epithelial tumors arising in the supracellar region infiltrating adjacent areas causing visual loss, panhypopituitarism, cognitive deficits and morbid obesity. Papillary craniopharyngiomas (PCP) harbour in 94% BRAF mutation. Two patients with PCP and BRAF V600E mutation but with different tumor status were treated with BRAF- and MEK-inhibitors. Case I, was diagnosed with biopsy, and treated for 16 months with BRAF- and MEK-inhibitors. After 3.5 months there was a 50% reduction of the tumor volume, and after 13 months the tumour volume decreased from 2220 mm3 to 90 mm3 (96%). Two months after stopping the drugs he was treated with fractionated cranial irradiation (54 Gy). No recurrence of the PCP was recorded. Eight months after stopping the drugs, he was diagnosed with an adenocarcinoma of the oesophagus, which led to his death 12 months later. Case II a woman had had four surgeries due to recurrences of a PCP and a BRAF V600E mutation was confirmed. After a new recurrence measuring 14x12x18 mm she was started on BRAF- and MEK-inhibitors. After 4 months of treatment a significant decrease to 8x9x13 mm was recorded. The treatment continued for 31 months and the MRI demonstrated a stable unchanged size including scar tissue, with a volume reduction from 633 mm3 to 483mm3. During treatment her visual acuity improved in her left eye from 0.05 to 0.3. After stopping the drugs “watchful waiting” with repeated MRI was decided. She is now off treatment since 25 months, without any recurrence on MRI.