Concurrent Radiation and Targeted Therapy for Papillary Craniopharyngioma: A Case Report

Craniopharyngiomas are rare epithelial malformations in the sellar or suprasellar regions of the craniopharyngeal ducts. Complete surgical resection is difficult due to the location of the base of the skull and the risk of injury to vital neurological structures. Fractionated radiation is effective in controlling residual tumors, but craniopharyngiomas can progress during treatment. The papillary subtype is driven by BRAF V600E mutations. Treatment with BRAF and MEK inhibitors alone has a response rate of 90% but a median progression-free survival of only 12 months. A 57-year-old female presented in May 2017 with complaints of headaches and blurriness in her right eye. Brain MRI demonstrated a 2 cm suprasellar mass engulfing the right optic nerve and optic chiasm. The patient underwent a transsphenoidal hypophysectomy with pathology consistent with a benign pituitary adenoma. Follow-up imaging in August, however, showed recurrence, and a re-resection was performed which surprisingly demonstrated papillary craniopharyngioma. Due to subtotal resection, the patient elected to proceed with intensity-modulated radiation therapy (IMRT) to the tumor bed in April of 2018 with an intended dose of 5400 cGy. After treatment with 2160 cGy in 12 fractions, the patient experienced visual deterioration and progression of the cystic tumor. The patient underwent another debulking procedure but due to rapid recurrence, an endoscopic transsphenoidal fenestration was performed. On postoperative imaging, a cystic mass was still engulfing the right optic nerve and chiasm. Due to the extended break and limited radiation tolerance of the optic chiasm, we elected to re-treat the tumor with an additional 3780 cGy IMRT in conjunction with one cycle of Taflinar and Mekinist, which was completed in August 2018. The cumulative dose to the optic chiasm was 5940 cGy.The patient had an excellent clinical response to treatment with the improvement of vision in her right eye. A brain MRI on 3/29/2019 demonstrated no residual craniopharyngioma. Four-year follow-on CT scan showed no evidence of tumor recurrence. The patient had preservation of vision and did not suffer any late neurological toxicity or new endocrine deficiency. Surgical resection and radiation were ineffective at treating our patient's craniopharyngioma due to rapid cystic progression. This is the first case report in the literature detailing concurrent radiation therapy with BRAF and MEK inhibitors for papillary craniopharyngioma. Despite a suboptimal dose of radiation, our patient had no tumor recurrence and no late toxicity four years after treatment. This represents a potentially novel treatment strategy in this challenging entity.