LGG-07. Is Braf Alteration or a Histologic ‘Qualifier’ a Predictor of Outcome in Pediatric Pilocytic Astrocytoma?

Abstract

Introduction Pediatric pilocytic astrocytomas (PA) are the most common pediatric central nervous system tumor. Surgical resection is the primary treatment for PA with five-year survival rates up to 95%. Despite a favorable prognosis, our understanding about the prognostic value of histopathological findings, such as histopathologic qualifier* or BRAF alterations is evolving. Methods Patients treated for a WHO grade 1 PA at Washington University in St. Louis/St. Louis Children’s Hospital were analyzed for clinical details, including pathology diagnosis (*histopathologic qualifier refers to designations in the diagnosis such as “WHO Grade I pilocytic astrocytoma with increased proliferative index”). BRAF alterations include gene fusions and point mutations. Results 224 patients were analyzed (51% female, mean age 9.6 years). Tumors were located in the cerebellum/fourth ventricle (50%), optic pathway/hypothalamus (15%), brainstem (12%), and cerebral cortex (11%). BRAF alterations were identified in 55/77 patients (71.4%) and additional histopathologic qualifiers were present in 27/220 patients (12.3%). 196 patients (87.5%) underwent surgical treatment and 22 (9.8%) had biopsy alone. 45 patients (22%) displayed tumor progression or recurrence after resection. The presence of a histopathologic ‘qualifier’ in the topline or BRAF alteration was not associated with tumor progression or recurrence (p=0.36, p=0.77). Ki-67 proliferative indices were not predictive of progression or recurrence (p=0.94), including when controlling for extent of resection and adjuvant therapy. BRAF alterations, specifically KIAA1549 fusions, were associated with cerebellar/fourth ventricular tumor location (p<0.001) and younger patient age (p=0.03). Extent of resection was the only predictor of outcome identified in this study; patients with gross total resection had significantly lower rates of progression and recurrence (p<0.0001). Conclusion BRAF alterations and histopathologic qualifiers were not associated with tumor progression or recurrence in pediatric PA, although BRAF fusions were more common in tumors located in the cerebellum/fourth ventricle and in younger patients.