Primary adult retroperitoneal sarcoma (RS): Comprehensive genomic profiling (CGP) study.

Abstract

11541 Background: We performed CGP on 315 cases of RS to discover targetable genomic alterations (GA) and their potential impact on potential targeted and immunotherapy (IO) selection. Methods: FFPE tissues from 315 clinically advanced RS tissues underwent hybrid-capture based CGP (DNA and RNA). Tumor mutational burden (TMB) was determined on up to 1.2 Mbp of sequenced DNA, and tumor cell PD-L1 expression was determined by IHC (Dako 22C3) (low = 1-49%; High = >50% tumor cell staining). Results: 155 liposarcomas (LPS), 74 leiomyosarcomas (LMS), 46 pleomorphic sarcomas (PLS), 7 solitary fibrous tumors (SFT), 6 malignant peripheral nerve sheath tumors (MPNST), 5 synovial sarcomas (SS) and 5 dendritic follicular cell sarcomas (DFCS) were studied; 17 cases were excluded. Median age was 59. There were 5.1 GA/tumor, none were MSI-high, median TMB was low at 2.4; PD-L1 IHC staining was low-positive in 21% and high-positive in 5%. MPNST patients were younger (median 28 years vs. 59 years). LPS was more frequent in men and LMS in women. LPS had more GA/tumor than LMS, with DFCS having the highest and SS the lowest. TP53 and RB1 GA were the highest in LMS and CDK4/6 and MDM2 GA the highest in LPS. Molecular targets in mTOR pathway were most frequently altered. Targetable gene fusions in ALK, ROS1 and NTRK1-3 were rare. Non-targetable fusions in HMGA2 (LPS and some PLS), STAT6 (SFT) and SS18 (SS) were also identified. Conclusions: RS in our cohort are predominantly composed of LPS, LMS and PLS and we identified a small proportion with “actionable” genomic targets on CGP, albeit in association with uncertain mTOR pathway inhibitor benefit and uncommon targetable kinase fusions. Our analysis suggests that a small subset of RS may respond to immunotherapy based on putative biomarker expression. [Table: see text]