Ultrasound in the assessment of tumor response in the age of targeted and immuno-oncology therapies back to the future

In Oncology, ultrasound has been long considered among the least convincing imaging techniques to evaluate response to chemoteraphy. The inter-operator variability, reduced panoramic view, and the impossibility of providing information about lung and bones were justified reasons for considering computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) as superior techniques compared to ultrasound imaging (US). But should we accept this message as unequivocal and true for every possible clinical setting in Oncology and most importantly even for any future scenario? Most likely not. Inspite of the above mentioned limitations, US techniques have become able to provide additional informations that are complementary to those provided by other techniques. Our readers could undoubtedly think that this merit belongs to the technological development of that the ultrasound techniques have experienced in recent years, including contrast enhanced ultrasound and sonoelastography [1 – 3]. However, while this thought is undoubtedly correct, this paradigm shift is in addition derived from the parallel progress in the development of new anticancer drugs. The conventional cytotoxic regimens, whose efficacy is measured according to the extent of tumour shrinkage, have become flanked or replaced by targeted therapies that achieve disease stabilisation with a reduced rate of objective responses. Most often, this effect mirrors a reduction in intratumoral microvascular blood flow. Different clinical trials have evaluated the possibility of correlating CEUS parameters and clinical response to these new agents. Indeed, a correlation was demonstrated for patients with renal cell carcinoma (RCC) treated with sunitinib [4] and sorafenib [5, 6], for patients with hepatocellular carcinoma (HCC) treated with bevacizumab [7] and sorafenib [8], and for patients with liver metastases from neuroendocrine tumours [9]. In the case of HCC, CEUS obtained using vascular endothelial growth factor receptor-2 (VEGFR-2) targeted microbubbles was also explored in a murine model, resulting in a potential imaging modality to discriminate sorafenib responders and non-responders [10].