EPCO-54. GENETIC PROFILE OF SKULL BASE CHONDROSARCOMAS AND RESPONSE TO TREATMENT IN PATIENTS WITH IDH1 MUTATED TUMORS

Abstract

Abstract Chondrosarcomas are uncommon tumors, with an incidence of 0.1-0.3 cases per 100,000 people. Current treatment consists of maximal safe surgical resection. The addition of adjuvant radiation reduces 5-year mortality by about 50%, but recurrence rates at 5 years are still over 30%. Targeted treatment options are needed to improve outcomes for patients with these tumors. IDH catalyzes the oxidative carboxylation of isocitrate to produce a-ketoglutarate. IDH1 mutations been identified across multiple cancers, included gliomas, AML, cholangiocarcinomas, and chondrosarcomas. These mutations are thought to impair cell differentiation and lead to tumorigenesis. OBJECTIVES: We present 2 cases of IDH1 mutant skull base chondrosarcomas that were treated with an IDH inhibitor. Both patients had radiographic involution of their tumors with no progression 2 years later. We describe the genetic profile of chondrosarcomas, elucidate associations between tumor mutations and clinical course, and investigate the mechanism of treatment response. METHODS: We performed a retrospective cohort analysis of 38 patients with skull base chondrosarcomas. Cox proportional hazards models were performed. Whole exome sequencing (WES) was performed on tumor samples, including multiple samples taken at various time points during the clinical course in 3 patients. RESULTS: A total of 38 patients with skullbase chondrosarcomas underwent surgery between 2000 and 2020. Mean follow-up time was 83.3 ± 107.7 months. Mean progression free survival time was 54.4 ± 71.5 months. Mortality was 15.8%. WES was available for 29 patients. Of these, 22 patients had IDH1 mutations (75.9%). Of these 22, the most common amino acid change was at the R132C position (45.5%). There was a trend towards increased mortality in patients that were IDH1 wildtype (42.8%) vs IDH1 mutant (13.6%). CONCLUSION: While IDH1 mutations are possible therapeutic targets with exciting preliminary responses, treatment response is likely complex and dependent on multiple mutations. Further analyses and validation studies are underway.