Clinical, radiological and genetic features, associated with the histopathologic response to neoadjuvant chemotherapy (NAC) and outcomes in locally advanced soft tissue sarcoma (STS) patients (pts).

11014 Background: Two large phase III studies have shown an improved overall survival in soft-tissue sarcoma (STS) pts treated with neoadjuvant chemotherapy. The prognostic impact of pathologic response is not known neither the clinical, radiological and genetic features associated with response. Methods: Data from pts with localized STS of the extremities or trunk wall and treated with anthracyline-based NAC at Institut Bergonie (Bordeaux, France) were reviewed. Central pathology (diagnosis, histological response) and radiology (MRI, DCE-MRI) reviews were performed for all the cases. A good histological response (GR) was defined as <10% residual viable tumor. Exome and RNA sequencing of pre-treatment tumor samples was performed in order to identify genetic aberrations predictive of response. Results: 150 patients (88 male) were included in the study. Median age was 60 years (17-84). 40 pts (26.7%) were good responders. GR was associated with undifferentiated pleomorphic sarcomas and very large tumors (> 20 cm). Median OSwas 10.3 year [IC95 : 5.8 ; 14.9]. On multivariate analysis, only GR (HR= 0.36, 95%CI 0.184-0.703, p=0.0028) and performance status (PS) (HR= 3.799, 95%CI 1.72-8.387, p=0.001 for PS=2-3) were prognostic factors for OS. Early DCE- MRI parameters (after 2 cycles of treatment) such as, area under the contrast concentration vs. time curve for 90 seconds after contrast injection ( IAUC90) were strongly associated with histological response (p=0.027) whereas RECIST 1.1 was not. Conclusions: As for bone sarcomas, histological response to NAC is a crucial prognostic factor in STS. Multiparametric MRI parameters obtained post-2 nd cycle of NAC are predictive of histological response and should be considered to adjust the therapeutic strategy. Genetic features (including the CINSARC signature) associated with response to NAC will be presented at the meeting.