Translational study of the phase III randomized EORTC-62092 STRASS trial (TRANS-STRASS)
Patients with retroperitoneal sarcomas face a high risk of disease recurrence following surgery with curative intent. Approximately one-third of patients with well-differentiated liposarcoma (WDLPS) develop local recurrence, while nearly half of those with dedifferentiated liposarcoma (DDLPS) experience either local recurrence or distant metastasis or both. In contrast, leiomyosarcomas (LMS), another common retroperitoneal histology, predominantly recur at distant sites. For local recurrences, therapeutic options remain limited to surgery and palliative radiation, often resulting in poor outcomes. Distant metastases are treated with systemic chemotherapy, but specific therapies tailored to the unique biology of retroperitoneal sarcomas are lacking.
The EORTC-62092 STRASS randomized trial suggested that preoperative radiotherapy combined with surgery may reduce the risk of abdominal recurrence in WDLPS and DDLPS compared to surgery alone (PMID: 32941794). However, as this finding emerged from subgroup analysis, the overall effectiveness of preoperative radiotherapy in retroperitoneal liposarcomas remains debated. Furthermore, there is a critical unmet need for biomarkers to identify patients most likely to benefit from radiotherapy and for insights into mechanisms that could enhance radiotherapy efficacy.
This study aims to leverage pre-treatment biopsy and surgical specimen samples collected from patients in the EORTC-62092 STRASS trial to conduct a comprehensive translational research analysis. Using transcriptomic profiling, we will: i) identify biomarkers predictive of tumor response to radiotherapy; ii) detect upregulated druggable target genes following radiotherapy, offering opportunities for novel therapeutic approaches; iii) investigate changes in the tumor immune microenvironment to assess the potential for immune-based therapies; iv) validate prognostic transcriptomic signatures to improve the accuracy of existing staging tools.
This research represents the first effort to exploit these unique samples for a translational analysis within the context of the EORTC-62092 STRASS trial. The findings have the potential to refine patient selection for radiotherapy, identify actionable therapeutic targets, and pave the way for innovative treatment strategies to improve outcomes for patients with retroperitoneal sarcomas.