OS9.3 Clinical, molecular and radiomic profile of gliomas with FGFR3-TACC3 fusion. (6th September 2019)

• Record Type: Journal Article
• Authors: Picca, A; Alentorn, A; Saragoussi, E; Bielle, F; Ducray, F; Villa, C; Schmitt, Y; Lerond, J; Leclerc, J; Lasorella, A; Iavarone, A; Mokhtari, K; Savatovsky, J; Sanson, M; Di Stefano, A
• Is Part Of: Neuro-oncology. Volume 21(2019)Supplement 3
• Page Start: iii18
• Page End: iii19
• Publication Date: 2019-09-06
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noz126.061
• Languages: English
• ISSNs: 1522-8517

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.