Impact of PET/CT for Assessing Response to Immunotherapy—A Clinical Perspective

Abstract

Cancer immunotherapy using immune-checkpoint inhibitors (ICI) has revolutionized the therapeutic landscape of various malignancies like non-small-cell lung cancer or melanoma. Pre-therapy response prediction and assessment during ICI treatment is challenging due to the lack of reliable biomarkers and the possibility of atypical radiological response patterns. Positron emission tomography/computed tomography (PET/CT) enables the visualization and quantification of metabolic lesion activity additional to conventional CT imaging. Various biomarkers derived from PET/CT have been reported as predictors for response to ICI and may aid to overcome the challenges clinicians currently face in the management of ICI-treated patients. In this narrative review, experts in nuclear medicine, thoracic oncology, dermatooncology, hemato- and internal oncology, urological and head/neck tumors performed literature reviews in their respective field and a joint discussion on the use of PET/CT in the context of ICI treatment. The aims were to give a clinical overview on present standards and evidence, to identify current challenges and fields of research and to enable an outlook to future developments and their possible implications. Multiple promising studies concerning ICI response assessment or prediction using biomarkers derived from PET/CT alone or as composite biomarkers have been identified for various malignancies and disease stages. Of interest, additional major incentives in the field may evolve from novel tracers specifically targeting immune-checkpoint molecules which could allow not only response assessment and prognosis, but also visualization of histological tumor cell properties like programmed death-ligand (PD-L1) expression in vivo. Despite the broad range of existing literature on PET/CT-derived biomarkers in ICI therapy, implications for daily clinical practice remain elusive. High-quality prospective data are urgently warranted to determine whether patients benefit from the application of PET/CT in terms of prognosis. At the moment, the lack of such evidence as well as the absence of standardized imaging methods and biomarkers still precludes PET/CT imaging to be included in the relevant clinical practice guidelines.

Nanotechnology for Cancer Imaging: Advances, Challenges, and Clinical Opportunities

“…However, 18 F-FDG PET/CT cannot help differentiate tumors from the influx of inflammatory cells in response to an immunecheckpoint inhibitor (80). Anti-programmed death 1 activation can stimulate the upregulation of GLUT messenger RNA and GLUT proteins in the tumor microenvironment, leading to glucose consumption and increasing false-positive scanning results (81). The feasibility of using PET to quantify programmed death ligand 1 (PD-L1) levels in patients has been demonstrated with 89 Zr-labeled atezolizumab, but this method still has a high chance of false-positive results, possibly due to inflammation (82).…”

Quantitative FDG PET Assessment for Oncology Therapy

“…Positron emission tomography (PET) is a clinical tool that can measure the distribution of radioactivity concentration in a space and has high capability for quantitation [ 1 ]. PET with radiolabelled glucose analogue ( 18 F-fluorodeoxyglucose [FDG]) enables the visualization of metabolic rate of glucose in vivo [ 2 ].…”

Heterogeneous Response to Immunotherapy in a Patient with Tonsillar Squamous Cell Carcinoma Assessed by 18F-FDG PET/CT

“…To obtain a standardized, reproducible, and accurate PET evaluation of therapeutic response in solid tumors, analogous RECIST criteria have been suggested for functional imaging, such as the European Organization for Research and Treatment of Cancer (EORTC) PET Criteria or the PET Response Criteria in Solid Tumors (PERCIST), based on quantitative measurements of changes in glucose metabolism [ 12 , 13 ]. However, the optimal interval time between 18 F-FDG PET/CT and the last treatment is still a matter of debate [ 2 , 14 ].…”

“…As well as radiological assessment, atypical patterns also pose challenges in post-ICIs PET evaluation. Analogously, modified metabolic criteria have now been suggested for post-immunotherapy PET/CT study, such as iPERCIST, combining RECIST and PERCIST with the introduction of the “unconfirmed progressive metabolic disease” category, PERCRIT, PERCIMIT, and imPERCIST5 for melanoma patients or LYRIC for Hodgkin lymphoma [ 10 , 12 ]. However, further prospective studies need to validate these as standards for head and neck cancer patients.…”