Peer-review started: August 23, 2016
First decision: October 21, 2016
Revised: November 2, 2016
Accepted: November 27, 2016
Article in press: November 29, 2016
Published online: February 28, 2017
Processing time: 191 Days and 12 Hours
Strategies targeting intracellular negative regulators such as immune checkpoint inhibitors (ICPIs) have demonstrated significant antitumor activity across a wide range of solid tumors. In the clinical practice, the radiological effect of immunotherapeutic agents has raised several more relevant and complex challenges for the determination of their imaging-based response at single patient level. Accordingly, it has been suggested that the conventional Response Evaluation Criteria in Solid Tumors assessment alone, based on dimensional evaluation provided by computed tomography (CT), tends to underestimate the benefit of ICPIs at least in a subset of patients, supporting the need of immune-related response criteria. Different from CT, very few data are available for the evaluation of immunotherapy by means of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, since the antineoplastic activity of ICPIs is highly related to the activation of T cells against cancer cells, FDG accumulation might cause false-positive findings. Yet, discrimination between benign and malignant processes represents a huge challenge for FDG-PET in this clinical setting. Consequently, it might be of high interest to test the complex and variegated response to ICPIs by means of PET and thus it is worthwhile to ask if a similar introduction of immune-related PET-based criteria could be proposed in the future. Finally, PET might offer a new insight into the biology and pathophysiology of ICPIs thanks to a growing number of non-invasive immune-diagnostic approaches based on non-FDG tracers.
Core tip: In the clinical practice, the radiological interpretation of immunotherapy effects represents a huge challenge at single patient level. However, although the computed tomography-based response evaluation for immune checkpoint inhibitors (ICPIs) is feasible thanks to the introduction of immune-related response criteria, very few data are available for the potential role of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Due to the intrinsic nature of FDG accumulation pathophysiology, it might be central to test the complex and variegated response to ICPIs by means of PET. Finally, PET might offer a new insight into the biology of ICPIs thanks to a growing number of non-invasive immune-diagnostic approaches based on non-FDG tracers.