OS9.3 Clinical, molecular and radiomic profile of gliomas with FGFR3-TACC3 fusion

Abstract

Abstract PURPOSE Actionable oncogenic fusion FGFR3-TACC3 (F3T3) is found in 3% of gliomas. Our goal was to characterize the clinical, radiological and molecular features of patients with F3T3-positive glioma. PATIENTS AND METHODS Overall, we screened 1112 gliomas by RT-PCR (861 WHO grade IV, 140 grade III and 111 grade II) and identified 50 F3T3-positive cases. We performed a radiological and radiomic case control study. RESULTS F3T3 fusion was exclusively found in IDH wild-type gliomas. F3T3 was mutually exclusive with the EGFR amplification (0/38 versus 143/336 of F3T3-negative cases, P=0.01), whereas it was associated with CDK4 amplification (7/33 versus 22/321 of F3T3-negative cases, P=0.04) and MDM2 amplification (6/33 versus 15/354 of F3T3-negative cases, P=0.03). F3T3-positive gliomas showed a longer overall survival than F3T3-negative gliomas (median OS 40.1 and 20.0 months, P=0.02), particularly in the grade IV subgroup (40.1 versus 19.0 months, P=0.006). Multivariate analysis showed that F3T3 fusion is an independent predictor of favorable outcome for glioblastoma patients. F3T-positive gliomas were associated with involvement in non-eloquent areas (r=0.31 P=0.007), cortico-subcortical regions and insula involvement (adjusted p<0.001), poorly defined enhancing margins (r=0.48 P<0.001), poorly defined non-enhancing margins (r=0.61 P<0.001), and higher proportion of edema (r=0.43 P<0.001). Radiomics analysis correctly classified F3T3-positive glioma with an AUC of 0.82. We compared different Cox proportional hazards models using Harrel’s C-Index. Although radiomics alone obtained a high C-Index (0.75, SD 0.04), the model combining clinical, genetic and radiomic data showed the highest C-index (0.81, SD 0.04). CONCLUSION Gliomas harboring F3T3 gene fusions show specific molecular features, distinct radiological and radiomic features and a less aggressive clinical evolution.