(P 141) COMPREHENSIVE GENOMIC PROFILING OF PATIENTS DIAGNOSED WITH SARCOMA IN BRAZIL: MOLECULAR PROFILE AND ACTIONABILITY

Objective: Evidence from both retrospective and prospective studies underscore the significant impact of comprehensive genomic profiling (CGP) on clinical outcomes in sarcomas. CGP may aid in diagnosis, inform prognosis, and identify actionable targets for directed systemic treatments. This study reports data from sarcomas submitted to 3 different tests of somatic comprehensive genome profiling in a single high-volume center in Brazil.

Methods: We retrospectively collected clinical and genomic data of patients diagnosed with soft tissue sarcomas (STS), bone sarcomas (PBS), and gastrointestinal stromal tumors (GIST) who underwent CGP between January 2017 and September 2023. Three different tests were used according to physician discretion: the Oncomine Focus Assay, Illumina Trusight Oncology 500, and Foundation Heme.

Results: A total of 85 patients had tumor samples sent for CGP. The cohort consisted of 47 males and 38 females, with a median age of 51 years. STS were predominant (n=71), with sarcoma NOS, leiomyosarcoma, undifferentiated pleomorphic sarcoma, and angiosarcoma being the most frequent subtypes. There were 8 cases of PBS, including 4 osteosarcomas, and only 2cases of GIST. Tumor mutational burden (TMB) was higher than 10 mut/Mb in 4 samples, one of which was a chondrosarcoma that also presented high microsatellite instability. Oncogenic alterations were identified in 69 of 85 tumor samples (81%), with a total of 200 distinct oncogenic alterations detected. Of these, 48 were considered actionable. These actionable alterations were found in 30 tumor samples (35%). The OncoKB grading level of evidence ranged from 1 to 4, with 8 cases classified as grade 1 (17%) and 30 (62.5%) graded as OncoKB 4. The most commonly altered genes were TP53 and RB1. Gene amplifications, missense mutations, and fusions were the most common oncogenic alterations in this cohort

Conclusion: To the best of our knowledge, we provide the largest single-institution analysis of CGP in sarcoma in Latin America. Our study identified actionable alterations in 35% of tumor samples of 85 patients diagnosed with sarcoma submitted to CGP. A high level of evidence of clinical activity according to OncoKB criteria was noted in 17% of actionable alterations. Additionally, in this retrospective analysis, CGP has been used for diagnostic purposes, as many cases submitted for testing were classified as sarcomas not otherwise specified (NOS). These findings highlight the potential of CGP for the management of sarcoma. Future analysis of the same cohort will provide further insight into clinical endpoints and the influence of CGP on each case.