Abstract

Abstract BACKGROUND Patients with primary brain tumors usually have poor prognosis and few therapeutic options. However recent report showed that they may benefit from molecular screening to improve treatment benefit and enrollment in clinical trials. We aimed to evaluate if molecular screening using Foundation One Dx may help therapeutic strategies in primary brain tumor patients. MATERIAL AND METHODS Between October 2018 and December 2018, we enrolled prospectively patients in the MOSCATO (Molecular Screening for cancer Treatment Optimization) 02 trial using the Foundation One Dx test. Patients were eligible if they had good Performans status (PS) (0 or 1) and tumor tissue material available. Results were reviewed during a molecular multidisciplinary meeting weekly at the Drug Development Department at Gustave Roussy to decide on orientation and matched therapy according to molecular alterations. RESULTS Finally thirty-three patients were enrolled in the study. Twenty six tumor tissues were analysed and 7 patients were screen failures due to tumor tissue unavailability. Median age was 49 years old (19 - 72). Patients had a good PS with a median of 1 (0–2) and were mostly males (76%). The most common tumor type was glioblastoma (79%). Five patients had a high grade tumor including 2 medulloblastomas. Median time between consent and multidisciplinary meeting was 70 days (49 - 156). Median percentage of tumor cells was 78% (30–80%). The tumor mutational burden (TMB) was available in 26 patients. The median TMB was 4 mutations per megabase (0 - 277). The most frequent alterations were TERT promoter mutation 22/26 (85%), CDKN2A loss 14/26 (54%), MTAP loss 11/26 (42%), EGFR amplification (38%) including 4 EGFRvIII amplification, TP53 mutation and PTEN deletion 9/26 (35%) respectively, PIK3CA mutation 5/26 (19%), CDK4 or 6 amplification 4/26 (15%), NF1 mutation 3/26 (12%), 2 IDH1 mutations, 2 MET amplifications, 2 HGF amplifications, 1 FGFR2 mutation, 1 BRAF V600E mutation, 1 PDGFRA amplification, 1 EZH2 mutation and 1 SMARCA4 mutation. Finally 11 patients (42%) were oriented according to molecular alterations (EGFR amplifications, BRAF mutation), 1 patient was treated and is ongoing with a BRAF inhibitor and 1 patient is in screening in atrial with an EGFR inhibitor. CONCLUSION Molecular screening with Foundation One Dx test is feasible in patients with primary brain tumors and can help therapeutic strategies. However the time between consent and multidisciplinary meeting was the main limitation to our study and affected enrollment in clinical trials.

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