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The locally advanced marginally resectable primary soft tissue sarcomas (MRSTS) require neoadjuvant treatment before the attempt of surgery. The study aimed to assess genetic changes in MRSTS that may be predictive factors in MRSTS treatment.

We analysed preoperative core biopsy samples of 20 patients with MRSTS who received 5×5 Gy radiotherapy combined with three cycles of doxorubicin-ifosfamide chemotherapy in a phase II clinical trial (NCTXXXXXXXX). Enrolled patients included eleven patients with undifferentiated pleomorphic sarcoma (UPS), one patient with leiomyosarcoma (LMS), five patients with myxofibrosarcoma (MFS), one patient with pleomorphic liposarcoma (PLPS), one patient with dedifferentiated liposarcoma (DDLPS), one patient with malignant peripheral nerve sheath tumor (MPNST). The pathological response to neoadjuvant therapy was assessed using the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) recommendations for pathological examination and reporting. Next-Generation Sequencing (NGS) Illumina NGS TruSight Oncology 500 kit was used to assess over 500 genes.

The analyzed group presented a low tumor mutation burden and no microsatellite instability. The identified mutations were presented in Table 1. There were five patients with good response to therapy (A = 1, B = 1, C = 3) and 15 patients with poor response to therapy (D = 10, E = 5). All but one mutation with strong pathogenic prediction were found in poor responders to neoadjuvant radiochemotherapy (Table 1). An intronic mutation of TP53 was found in one patient with UPS who presented an excellent response to therapy.

Table 1. Results of molecular analysis

The detection of known mutations in MRSTS suggests poor pathological response to neoadjuvant radiochemotherapy. Identified mutations may indicate new therapeutic targets in the treatment of MRSTS.