Imaging response in neuroendocrine tumors treated with targeted therapies: the experience of sunitinib

Among neuroendocrine carcinomas of the gut, well-differentiated tumors are highly vascularized, featuring specific characteristics on contrast-enhanced imaging. Well-differentiated neuroendocrine tumors spontaneously harbor hypervascular enhancement, coexisting with areas of necrosis mainly located at the center of tumor lesions. When exposed to vascular endothelial growth factor (VEGFR) inhibitors such as sunitinib, target lesions display few if any variation in tumor size, but rather detectable modifications in tumor density. In several patients treated with targeted therapy, a significant decrease of tumor density at first tumor evaluation can be detected as compared to baseline. Consistently, the two randomized trials leading to approval of sunitinib and everolimus in pancreatic neuroendocrine tumors report objective response rate below 10%, emphasizing that Response Evaluation Criteria in Solid Tumors (RECIST), that focus only on the largest diameters of target lesions, may be insufficient to capture the full benefit of targeted therapies. Alternative criteria, such as those developed by Choi et al., consider both the size and the density of the tumor as parameters for response evaluation. Choi criteria have been recently proposed as a surrogate endpoint for efficacy and to identify patients that are good responders to VEGFR inhibitors such as sunitinib and sorafenib in advanced hepatocellular carcinoma, another disease highly addicted to angiogenesis. Preliminary data generated from patients included in the sunitinib phase III trial suggest that Choi criteria might also be considered as an alternative to RECIST to evaluate the effects of sunitinib in patients with advanced well-differentiated neuroendocrine tumors.