Quantitative Analysis of PET/CT Images of Immune Related Side Effects in Metastatic Melanoma Patients

New cancer treatment with immune-checkpoint inhibitors (ICIs) has changed the way patients with melanoma and a variety of other cancers are being treated. Based on many positive randomised controlled trials in metastatic and neo-/adjuvant setting, ICI agents targeting programmed death-1 (PD-1), programmed death ligand-1 (PD-L1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) have become invaluable in the treatment of different carcinomas. Many pivotal trials that showed efficacy and safety of ICIs were performed in malignant melanoma.

ICI can cause a different type of toxicity, called immune-related adverse events (irAEs), that can occur in any organ of the body. Though the exact pathophysiology is not completely understood, it is believed that irAEs are provoked by immune upregulation and inflammation. In general, they are less frequent compared to chemotherapy toxicities and usually low grade and manageable. However, they can be serious, life-threatening, and warrant hospital admission as well. Dangerous irAEs include myocarditis, myositis, and pneumonitis, among others. Due to the novel mechanism of action, unpredictable nature, and wide usage of this type of treatment in the future, there is urgent need for better control of these potentially dangerous side effects. Early recognition and treatment of irAEs are of great importance in successful management.

Positron emission tomography-computed tomography (PET/CT) with [18F]2fluoro-2-deoxy-D-glucose (18F-FDG) is a sensitive, non-invasive, and widely used method for diagnosis and evaluation of treatment efficacy of malignant melanoma. The combination of 18F-FDG-PET and CT allows for assessment of both functional and morphological status of the lesions, and so facilitates better clinical decisions and patient care during treatment. It is also a very sensitive method for recognising inflammation, that can be a signal of irAEs.

Quantitative analysis is a rapidly evolving field of PET/CT image analysis. It includes both radiomics and artificial intelligence. Quantitative analyses of medical images provide insight into hidden information about the image, which is usually not fully assessed by a nuclear medicine specialist (for example, information on the spatial heterogeneity of the tumour). Some studies have reported that quantitative analysis could predict efficacy of different cancer treatments. Quantitative image analysis in cancer response assessment is a rapidly expanding field, with the ultimate goal of clinical translation. However, in the specific instance of irAE diagnosis, it is not yet clear what role quantitative analysis of PET/CT scans can play.

The hypothesis is that quantitative analysis of PET/CT images provides more information on possible irAE, thus helping to treat these side effects more quickly and successfully. The association of quantitative PET/CT analysis with patient survival and the predictive value of an early-time point PET/CT scan in response to ICIs will be prospectively examined. The positive impact or irAE of autoimmune thyroiditis on the outcome of ICIs treatment will be also will be also evaluated.