Hodgkin lymphoma and imaging in the era of anti-PD-1/PD-L1 therapy

The assessment of treatment response is crucial for patient management since it guides further treatment or surveillance program. For the purpose of response evaluation in Hodgkin Lymphoma patients, contrast-enhanced CT (CECT) and fluorodeoxyglucose (FDG)–positron emission tomography (PET) were demonstrated to be the most reliable imaging modalities. Response criteria based on tumor size variations on CT and/or modification of tumor glycolytic metabolism on FDG PET have been designed for the assessment of response to chemotherapy and targeted molecular agents. The recent introduction of biological agents with immunological activity revealed the need for criteria revision and for novel biomarkers. The treatment response assessment using the standard criteria for defining anatomical or metabolic remission has been shown to be poorly fit for the immune checkpoint inhibitors since they may determine the “tumor flares”, a phenomenon that has not the same prognostic implications as progressive disease. Accordingly, the response evaluation criteria have been reviewed introducing as main novelty the concept of “pseudo-progression”. Furthermore, PD-1 blockade is not effective in all patients, and delayed or mixed tumor regression can be seen. Therefore, some biomarkers including the detection of PD-L1 on tumor cells, the identification of specific genetic signatures, the longitudinal track of the circulating cell-free DNA, and the imaged-derived parameters have been evaluated to predict response to anti-PD-1/PD-L1 therapy. The present paper reports the available evidence on the role of imaging in patients with HL and future directions for the investigations in the field, with the special focus on the treatment with immune checkpoint inhibitors. © 2018, Italian Association of Nuclear Medicine and Molecular Imaging.