Evaluation of Chemotherapy Response in Osteosarcoma Using Quantitative Ultrasound: A Pilot Study Relating Ultrasound Parameters to Molecular Response

Currently, the response to chemotherapeutic treatment for most solid tumors is assessed using the surgical specimen obtained after the tumor is surgically removed, following a whole chemotherapy cycle ( e.g. 8 weeks). Therefore, early detection of tumor response is of paramount importance. Parameters derived from the backscatter coefficient (BSC) and envelope statistics provide information on tissue microstructure and may therefore be of interest for monitoring therapies that induce morphological changes in the tumor. In this study, our objective was to detect ex vivo early response to chemotherapy in ex vivo murine osteosarcoma model. BSC-derived parameters using Lizzi-Feleppa approach and the Gaussian model and envelope statistic parameters using Nakagami and Homodyned-K distributions were extracted on control and treated tumors. Tumors received either 2, 4, or 5 doses of chemotherapy. To investigate the underlying causes of changes in ultrasound parameters, histological and molecular analyses (RNA sequencing) were conducted. Although the tumor models show resistance to chemotherapy as evidenced by continued tumor growth at the therapeutic dose used, significant differences between treated and control tumors were observed in several BSC-derived and envelope statistics parameters depending on the number of treatments received. These differences might reflect early molecular changes occurring before the establishment of chemoresistance mechanisms. They might be attributed to morphological changes linked to the underexpression of genes involved in chromatin condensation and/or collagen within the extracellular matrix. These initial findings require further investigation in a larger cohort. • QUS detects early response to chemotherapy in murine osteosarcoma. • BSC and envelope statistics show differences between treated and controls. • Changes detected despite tumor growth indicate early molecular alterations. • RNA-seq links changes to chromatin and extracellular matrix remodeling.