Immunotherapy treatment: an issue for metabolic response.

Since the beginning of second decade of last century, when it was introduced in many oncologic scenarios, immunotherapy has become an important tool in the management of a growing number of cancers. Immunotherapy for cancer appears to be useful, improving not only progression free survival but also overall survival, thus achieving the goal that many advanced cancers, previously considered without effective treatment options, have now become successfully treatable. However, considering the relatively recent introduction of these drugs in clinical scenarios and the continuous release of new drugs, there is a lack of large validated clinical experiences and many issues are today debated amongst which the evaluation of the response to immune-therapy. Engaging the host immune system in fighting against cancer is an energy-consuming process, requiring T-cell recruiting; this process, named "pseudo-progression," sometimes produces an increase of both dimensional and metabolic ratio of the lesions, as well as the appearance of "new lesions." This behavior, always considered as undisputed progressive disease when traditional chemotherapy is employed, should be carefully considered in the field of immunotherapy, where the phenomenon of "flare" followed by regression of the disease can occur. In this paper, Authors analyzed the best available evidence in this field, reviewed the most important issues concerning the development of immunotherapy, and addressed evidence and concerns about the evaluation of response when using immunotherapy drugs, in terms of both radiological and nuclear medicine criteria.