Next-generation sequencing in patients with liposarcoma and rhabdomyosarcoma.

e23527 Background: Identifying targetable oncogenic drivers and resistance mechanisms by Next-generation sequencing (NGS) is critical in most cancers, including rare soft tissue sarcomas (STS) like liposarcoma (LPS) and rhabdomyosarcoma (RMS). Methods: We conducted an IRB-approved retrospective study at Sylvester Cancer Center to assess NGS use in STS, focusing on LPS and RMS. Medical records from January 2015 to June 2024 were reviewed, and data on demographics, cancer stage, NGS, and survival were collected. Cox Regression Analysis calculated the odds ratios for metastasis at initial presentation, treatment progression, remission after initial intervention, and mortality. Results: NGS was evaluated in 50 out of 117 LPS patients and 35 out of 48 RMS cases. The majority of patients were white and non-Hispanic ethnicity in both LPS and RMS data (88%; 72% vs 71.4%; 51.4%, respectively). Most LPS cases were 54% dedifferentiated, followed by 16% pleomorphic pathology. 60% of cases had progression of LPS on treatment, 52% had distant metastasis, and mortality was 42%. In RMS, 57.2% had progressive disease, 62.8% had distant metastasis and 45.7% mortality. Remission after initial intervention was found in 22.9% of LPS and 24% of RMS cases with NGS. Sixty-four mutations were found in LPS NGS cases, with the CDK4 gene being the most common. TP53 mutation was associated with distant metastasis (OR = 4.89; p = 0.06) and progression (OR = 15.6; p = 0.03) in LPS. FRS2 was associated with remission (OR = 12.8; p = 0.03) after initial treatment with surgery alone or combined with radiation and/ or chemotherapy. In RMS cases with NGS, TP53 was the most commonly mutated gene. Targetable mutation with PI3Kinase/PTEN and FGFR genes were observed at 6.4% and 5.5%, respectively. Subgroup analysis based on histology with LPS and RMS is pending and will be updated by April 2025. Conclusions: TP53 is associated with a higher risk of distant metastasis at initial presentation and progression of disease despite treatment. Given the rarity of LPS and RMS, further research is needed to explore the prognostic utility of mutations. STS Type Most common reported genetic variant Percentage Metastasis at presentation Progression despite treatment Remission after initial treatment Mortality related to STS OR p OR p OR p OR p LPSNGS reported in 42.7% cases (50/117) CDK4 16.50% 1.81 0.39 4.1 0.13 - - 0.62 0.28 MDM2 15.90% 1.6 0.41 1.5 0.56 - - 1.52 0.48 HMGA2 6.80% 1.06 0.93 1.2 0.82 1.93 0.52 0.98 0.98 TP53 5.70% 4.89 0.06 15.6 0.03 0.41 0.39 2.5 0.21 FRS2 3.40% 0.18 0.17 0.34 0.28 12.8 0.03 0.8 0.85 RMSNGS reported in 72.9% cases (35/48) TP53 13.40% 4.01 0.08 3.36 0.11 0.39 0.35 1.71 0.44