Peer-reviewed article

LGG-02. PEDIATRIC LOW-GRADE GLIOMA RISK STRATIFICATION IN THE MOLECULAR ERA

Hata J, Barbour M, Huang M · 1 Jun 2021

Abstract

Abstract Background Pediatric low-grade gliomas (LGG), in particular those not amenable to surgical resection, are a therapeutic challenge owing to their heterogeneity in clinical behavior. Identification of the RAS/MAPK pathway as a universal feature of these tumors has led to an improved understanding and the development of targeted therapeutics. We examined the impact of known biological and novel molecular risk factors on patient outcomes at our institution. Methods We retrospectively reviewed risk factors and clinical outcomes in 38 LGG cases diagnosed by histopathology at Norton Children’s Hospital in Louisville, KY, USA from March 2015 to Jan 2019. Progression free survival (PFS) rates were generated using the Kaplan-Meier method. Log-rank tests and hazard ratios were used to identify prognostic factors by univariable analysis. Results Among previously described biological risk factors, subtotal resection/biopsy only (HR 3.67, p=0.0257), non-WHO Grade I histology (HR 3.34, p=0.0101), and infant age (< 3 years) (HR 4.19, p=0.0031) were associated with shorter PFS. Brainstem location had no significant impact on PFS. (HR 0.86, p=0.8071). H3K27M mutant status was predictably associated with worse PFS (HR 5.86, p=0.0012). BRAF v600e mutant status, however, was not associated with inferior outcomes. On the contrary, in our study population, BRAF v600e mutant status had a suggested protective effect (HR 0.14, p=0.0247). Patients with 2 or more oncogenic driver mutations demonstrated worsened PFS (HR 4.78, p=0.0059). We utilized the following scoring system for risk stratification: 1 point was allocated for each of the above biological and molecular risk factors except for H3K27M, which was allocated 3 points. A score of < 3 was designated low risk. Non-low risk classification was associated with significantly inferior PFS (median PFS 13 vs. 62 mos, HR 4.26, p=0.0012). Conclusion We herein demonstrate the utility of a combined biological and molecular risk classification for pediatric LGG.