Tumor monitoring and detection of lymph node metastasis using quantitative ultrasound and immune cytokine profiling in dogs undergoing radiation therapy: a pilot study

Abstract: Quantitative ultrasound (QUS) characterizes the composition of cells to distinguish diseased from healthy tissue. QUS can reflect the complexity of the tumor and detect early lymph node (LN) metastasis ex vivo. The objective in this study was to gather preliminary QUS and cytokine data from dogs undergoing radiation therapy and correlate QUS data with both LN metastasis and tumor response. Spontaneous solid tumors were evaluated with QUS before and up to one year after receiving RT. Additionally, regional LNs were evaluated with QUS in vivo, then excised and examined with histopathology to detect metastasis. Paired t-tests were used to compare QUS data of metastatic and non-metastatic LNs within patients. Furthermore, paired t-tests compared pre- versus post-RT QUS data. Serum was collected at each time point for cytokine profiles. Most statistical tests were underpowered to produce significant $p$ values, but interesting trends were observed. The lowest $p$ values for LN tests were found with the envelope statistics $K$ ($p = 0.142$) and $\mu$ ($p = 0.181$), which correspond to cell structure and number of scatterers. For tumor response, the lowest $p$ values were found with $K$ ($p = 0.115$) and $\mu$ ($p = 0.127$) when comparing baseline QUS data with QUS data 1 week after RT. Monocyte chemoattractant protein 1 (MCP-1) was significantly higher in dogs with cancer when compared to healthy controls ($p = 1.12$e-4). A weak correlation was found between effective scatterer diameter (ESD) and Transforming growth factor beta 1 (TGF$\beta$-1). While statistical tests on the preliminary QUS data alone were underpowered to detect significant differences among groups, our methods create a basis for future studies.