pyrimidinones and Pituitary-Neoplasms

The BRAF-V600E genetic mutation offers a potential targeted therapy for the treatment of papillary craniopharyngiomas.. A 35-year-old man underwent a craniotomy and subtotal resection of a large BRAF-V600E-positive papillary craniopharyngioma before referral to our institution. Our treatment included the BRAF-V600 inhibitor dabrafenib mesylate (75 mg, twice/day) and trametinib dimethyl sulfoxide (2 mg/day). The residual tumour decreased in size by 95% over 21 months without negative side effects.. We reviewed the literature on BRAF-V600E inhibition as a non-invasive method of treating papillary craniopharyngiomas harbouring the BRAF-V600E mutation.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Craniopharyngioma; Humans; Male; Mutation; Oximes; Pituitary Neoplasms; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Pyridones; Pyrimidinones

Topics: Adenoma, Oxyphilic; Antineoplastic Agents; Humans; Imidazoles; Male; Middle Aged; Molecular Targeted Therapy; Mutation; Oximes; Pituitary Neoplasms; Proto-Oncogene Proteins B-raf; Pyridones; Pyrimidinones; Thyroid Nuclear Factor 1

We present a patient with BRAF-V600E mutant papillary craniopharyngioma successfully treated with combination BRAF (dabrafenib 150 mg twice daily) and MEK (trametinib 2 mg daily) inhibitors after her unresectable tumor proved refractory to radiation. Serial brain MRIs and PET revealed marked tumor reduction with gradual neurological improvement and permanent panhypopituitarism.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Craniopharyngioma; Female; Humans; Imidazoles; Middle Aged; Mutation; Oximes; Pituitary Neoplasms; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Pyridones; Pyrimidinones

Craniopharyngiomas are histologically benign but locally aggressive tumors in the sellar region that may cause devastating neurological and endocrine deficits. They tend to recur following surgery with high morbidity; hence, postoperative radiotherapy is recommended following sub-total resection. BRAFV600E mutation is the principal oncogenic driver in the papillary variant of craniopharyngiomas. Recently, a dramatic tumor reduction has been reported in a patient with BRAFV600E mutated, multiply recurrent papillary craniopharyngioma using a combination therapy of BRAF inhibitor dabrafenib and MEK inhibitor trametinib. Here, we report on near-radical reduction of a growing residual BRAFV600E craniopharyngioma using the same neoadjuvant therapy.

Topics: Aged; Craniopharyngioma; Humans; Imidazoles; Male; Molecular Targeted Therapy; Mutation; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Oximes; Pituitary Neoplasms; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Pyridones; Pyrimidinones; Sella Turcica

We recently reported that BRAF V600E is the principal oncogenic driver of papillary craniopharyngioma, a highly morbid intracranial tumor commonly refractory to treatment. Here, we describe our treatment of a man age 39 years with multiply recurrent BRAF V600E craniopharyngioma using dabrafenib (150mg, orally twice daily) and trametinib (2mg, orally twice daily). After 35 days of treatment, tumor volume was reduced by 85%. Mutations that commonly mediate resistance to MAPK pathway inhibition were not detected in a post-treatment sample by whole exome sequencing. A blood-based BRAF V600E assay detected circulating BRAF V600E in the patient's blood. Re-evaluation of the existing management paradigms for craniopharyngioma is warranted, as patient morbidity might be reduced by noninvasive mutation testing and neoadjuvant-targeted treatment.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Craniopharyngioma; Craniotomy; Cytoreduction Surgical Procedures; Drug Administration Schedule; Glutamic Acid; Humans; Imidazoles; Magnetic Resonance Imaging; Male; Molecular Targeted Therapy; Mutation; Neoplasm Recurrence, Local; Neoplasm, Residual; Oximes; Pituitary Neoplasms; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Pyridones; Pyrimidinones; Treatment Outcome; Valine