[18F]FDG PET/CT in the Evaluation of Melanoma Patients Treated with Immunotherapy

Abstract

Immunotherapy is based on manipulation of the immune system in order to act against tumour cells, with growing evidence especially in melanoma patients. The challenges faced by this new therapeutic tool are (i) finding valid evaluation criteria for response assessment; (ii) knowing and distinguishing between “atypical” response patterns; (iii) using PET biomarkers as predictive and response evaluation parameters and (iv) diagnosis and management of immunorelated adverse effects. This review is focused on melanoma patients analysing (a) the role of [18F]FDG PET/CT in the mentioned challenges; (b) the evidence of its efficacy. For this purpose, we performed a review of the literature, including original and review articles. In summary, although there are no clearly established or globally accepted criteria, modified response criteria are potentially appropriate for evaluation of immunotherapy benefit. In this context, [18F]FDG PET/CT biomarkers appear to be promising parameters in prediction and assessment of response to immunotherapy. Moreover, immunorelated adverse effects are recognized as predictors of early response to immunotherapy and may be associated with better prognosis and clinical benefit.

Metabolic Profiling to Assess Response to Targeted and Immune Therapy in Melanoma

“…Studies have also investigated the use of 18 FDG-PET as an early predictor of immune checkpoint blockades in patients with melanoma [140,141]. As an example, 18 FDG-PET performed after two cycles of ipilimumab has demonstrated high predictability for the final treatment outcome in patients with progressive and stable metabolic disease in metastatic melanoma.…”

“…However, the distinction of patients between pseudo-progression and progressive disease has been shown in several consecutive studies to be limited using 18 F-FDG-PET/CT, consisting of the combination of PET imaging with computed tomography (CT), providing anatomical information simultaneously with the 18 FDG uptake maps [142,143]. All studies assessing response to immunotherapy with 18 FDG-PET along with associated standardized evaluation criteria were recently reviewed by Mangas Losada et al [141]. Importantly, in 2018, standardized criteria, PERCIMT (PET Response Evaluation Criteria for Immunotherapy), were defined for melanoma, including morphologic and metabolic response to assess the clinical benefit of immunotherapy [141,144,145].…”

“…All studies assessing response to immunotherapy with 18 FDG-PET along with associated standardized evaluation criteria were recently reviewed by Mangas Losada et al [141]. Importantly, in 2018, standardized criteria, PERCIMT (PET Response Evaluation Criteria for Immunotherapy), were defined for melanoma, including morphologic and metabolic response to assess the clinical benefit of immunotherapy [141,144,145]. In parallel, standard PERCIST (Positron Emission tomography Response Criteria in Solid Tumors) criteria were also revisited in the scope of immunotherapy, including iPERCIST [146] and immunotherapy-modified PERCIST5 (imPERCIST) [147].…”

“…In parallel, standard PERCIST (Positron Emission tomography Response Criteria in Solid Tumors) criteria were also revisited in the scope of immunotherapy, including iPERCIST [146] and immunotherapy-modified PERCIST5 (imPERCIST) [147]. Although these criteria are neither globally accepted nor clearly established yet, they consider the fact that immunotherapy can cause non-conventional patterns of response and must be considered for personalized evaluation [141]. Despite the efforts that have been made to standardize the criteria to assess response to immunotherapy with 18 FDG-PET, many challenges remain in the field, including the distinction between atypical response patterns, including pseudo-progressive disease, hyper-progressive disease, dissociated response, and sustained response [145].…”

Prospective Assessment of Fluorine-18-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT) for Early Identification of Checkpoint-Inhibitor-Induced Pseudoprogression

“…ICI-related PsPD is observed in 10–15% of patients with melanomas. However, most patients with initial progression will have true PD and not PsPD [ 3 , 4 , 5 ]. Tools for early identification of true PsPD could greatly improve the management of patients treated with ICI, leading to timely discontinuation, reduced toxicity, and a possible shift in treatment.…”