A Clinical Rule for Preoperative Prediction of BRAF Mutation Status in Craniopharyngiomas

• Published in: Neurosurgery Vol. 85; no. 2; pp. 204 - 210
• Main Authors: Fujio, Shingo, Juratli, Tareq A, Arita, Kazunori, Hirano, Hirofumi, Nagano, Yushi, Takajo, Tomoko, Yoshimoto, Koji, Bihun, Ivanna V, Kaplan, Alexander B, Nayyar, Naema, Fink, Alexandria L, Bertalan, Mia S, Tummala, Shilpa S, Curry, William T, Jones, Pamela S, Martinez-Lage, Maria, Cahill, Daniel P, Barker, Fred G, Brastianos, Priscilla K
• Format: Journal Article
• Language: English
• Published: United States Copyright by the Congress of Neurological Surgeons 01.08.2019; Oxford University Press; Wolters Kluwer Health, Inc
• Subjects: Adolescent; Adult; Aged; Calcification; Care and treatment; Craniopharyngioma - genetics; Craniopharyngioma - pathology; Development and progression; Female; Gene mutations; Genetic aspects; Health aspects; Humans; Male; Middle Aged; Molecular Targeted Therapy - methods; Mutation; Neoadjuvant Therapy - methods; Neurosurgery; Patient Selection; Pituitary gland tumors; Pituitary Neoplasms - genetics; Pituitary Neoplasms - pathology; Proto-Oncogene Proteins B-raf - genetics; Sensitivity and Specificity; Tumors; United States; Papillary; Craniopharyngioma; Clinical rule; Prediction; BRAF V600E mutation
• ISSN: 0148-396X; 1524-4040
• DOI: 10.1093/neuros/nyy569

Papillary craniopharyngiomas are characterized by BRAFV600E mutations. Targeted therapy can elicit a dramatic radiographic regression of these tumors. Therefore, prediction of BRAF mutation status before definitive surgery could enable neoadjuvant treatment strategies. To establish preoperative prediction criteria to identify patients with a BRAF mutant craniopharyngioma. Sixty-four patients with craniopharyngioma were included in this study. We determined BRAF mutation status by targeted sequencing. After scoring interobserver variability between presurgical clinical data and radiographic features, we established a diagnostic rule for BRAF mutation in our discovery cohort. We then validated the rule in an independent cohort. The BRAFV600E mutation was detected in 12 of 42 patients in the discovery cohort. There were no patients under age 18 with BRAF mutation. Calcification was rare in tumors with BRAF mutation (P < .001), and 92% of them were supradiaphragmatic in location. Combining these 3 features-older than 18 years, absence of calcification, and supradiaphragmatic tumor location-we established a rule for predicting BRAF mutation. In cases where all 3 criteria were fulfilled, the sensitivity and specificity for the presence of BRAF mutation were 83% and 93%, respectively. In the validation cohort (n = 22), the sensitivity was 100% and specificity was 89%. We propose predictive criteria for a BRAF mutation in craniopharyngioma using preoperative clinical and radiographic data. This rule may be useful in identifying patients who could potentially benefit from neoadjuvant BRAFV600E-targeted systemic therapies.