Use of quantitative dynamic contrast-enhanced ultrasound to assess response to antiangiogenic therapy in children and adolescents with solid malignancies: A pilot study

OBJECTIVE. The purpose of this study was to investigate contrast-enhanced ultrasound assessment of tumor response to antiangiogenic therapy in children and adolescents with solid malignancies. SUBJECTS AND METHODS. Children with recurrent solid tumors who were enrolled in an institutional phase 1 study of antiangiogenic therapy underwent contrast-enhanced ultrasound of target lesions before therapy, on therapy days 3 and 7, and at the end of course 1. Acoustic data from target lesion ROIs were used to measure peak enhancement, time to peak, rate of enhancement, total AUC, AUC during wash-in (AUC1), and AUC during washout (AUC2). The Cox regression model was used to assess the association between changes in parameters from baseline to follow-up time points and time to tumor progression. Values of p ≤ 0.050 were considered significant. RESULTS. Target lesion sites included liver (n = 3), pleura (n = 2), and supraclavicular mass, soft-tissue component of bone metastasis, lung, retroperitoneum, peritoneum, lymph node, muscle mass, and perineum (n = 1 each). Hazard ratios for changes from baseline to end of course 1 for peak enhancement (1.17, p = 0.034), rate of enhancement (3.25, p = 0.029), and AUC1 (1.02, p = 0.040) were significantly associated with time to progression. Greater decreases in these parameters correlated with longer time to progression. CONCLUSION. Contrast-enhanced ultrasound measurements of tumor peak enhancement, rate of enhancement, and AUC1 were early predictors of time to progression in a cohort of children and adolescents with recurrent solid tumors treated with antiangiogenic therapy. Further investigation of these findings in a larger population is warranted.