Over the last decade, several strategies have revolutionized the clinical management of patients with lung cancer, including immunotherapy. Indeed, immune checkpoint inhibitors (ICI) monotherapy or in combination represent the standard-of-care for patients with advanced disease with no actionable mutation.

Due to the unique action of ICI to potentiate the immune system, conventional response assessment criteria in medical imaging, such as RECIST 1.1, have limitations. Unlike chemotherapy, patients treated with ICI can present atypical response patterns including pseudoprogression, hyper-progression, and dissociated response. Therefore, the creation and implementation of novel standardized response criteria that consider these distinct response patterns is of critical importance.

In parallel, FDG PET/CT is now part of the routine staging for patients with nonsmall cell lung cancer. Moreover, there is an increasing interest in using FDG PET/CT metrics for predicting response to ICI therapy. While standardized uptake values are limited in predicting outcomes, new metrics including tumor metabolic volume, total lesion glycolysis, metabolic activity of the gut microbiome, and radiomics show promise as potential nuclear-medicine ICI biomarkers. Moreover, PET tracers that specifically target immune checkpoints such as PD-L1 also showed promising results in predicting ICI response.

Finally, despite achieving higher response rates, ICI therapy leads to the development of immune-related adverse events such as pneumonitis or colitis. Therefore, it is of upmost importance for the imaging specialist to recognize the metabolic patterns associated with these new toxicity profiles.

In this paper, we will review how the FDG PET/CT can potentially become a useful marker for the evaluation of ICI response.