Establishing the predictive value of FDG PET/CT for response to ICI in metastatic melanoma and non-small cell lung cancer

Immune checkpoint inhibitors FDG PET/CT Immune-related adverse events

Dr. T.J.N. Hiltermann
F. Bensch
L.B.M. Hijmering

Nature of the research:
Retrospective data collection of patients treated with immune checkpoint inhibitors for metastatic melanoma and NSCLC

Fields of study:

Background / introduction
In the last decade the treatment of many cancers has changed fundamentally due to the introduction of immune checkpoint inhibitors (ICI). The addition of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death-ligand 1 (PD-L1) checkpoint inhibitors to standard of care in metastatic melanoma and NSCLC has led to substantial improvement of overall survival including earlier unseen durable responses. Initially, PD-L1 status assessed on a tumor biopsy was thought to be a good marker for patient selection. However, multiple studies reported responses also in PD-L1 negative patients, as well as failure of treatment in a substantial proportion of PD-L1 positive patients. Adequate biomarkers to preselect patients for immune checkpoint inhibitors are the key to a future of personalized medicine.

FDG-PET/CT is the standard imaging modality for staging of NSCLC and melanoma. Furthermore, tumor FDG-uptake is often used to assess response during therapy with ICI next to CT-based response criteria. Traditionally, response to therapy in NSCLC and melanoma is evaluated with the Response Evaluation Criteria in Solid Tumors (RECIST). However, responses in patients treated with ICI may show different response patterns compared to standard chemotherapy: Besides classic progression, stable disease and response to treatment, in some patients an initial increase of the tumor burden followed by a decrease as therapy continues can be seen, the so called pseudo-progression. To account for this phenomenon, several other standardized criteria such as the immune-related RECIST (irRECIST), the modified RECIST for immune-based therapeutics (iRECIST) and the PET response criteria in solid tumors (PERCIST) have been proposed to assess response to ICI. Clinical use, however, is difficult as no gold standard exist and measurements need to by repeated frequently, including an obligatory conformation after disease progression .

Since FDG-PET visualizes glucose metabolism, it can detect not only tumor cells, but also activated immune cells in and around the tumor, as well as in the rest of the body. As consequence, inflammatory side effects induced by ICI treatment, such as colitis (1), arthritis, Sjögren’s syndrome and thyroiditis, can be visualized by FDG-PET. Earlier studies have shown that the occurrence of ICI related side effects may be a positive predictor for a favorable outcome. Considering this, the presence of elevated FDG uptake in organs known to be susceptible for immune related side effects in patients treated with ICI may be an indicator of response.

In this retrospective, single center PET imaging analysis we want to assess whether the FDG uptake in different non-tumor tissues, as surrogate for the patients inflammatory state, is predictive for response to ICI. Furthermore, we will evaluate whether we can predict the occurrence of ICI related side effects by baseline FDG uptake of relevant tissues.
Research question / problem definition
Can we predict response to ICI treatment by measuring the body’s inflammatory state by means of FDG-PET?
Can FDG-PET aid as tool to identify immune-related adverse events in patients with metastatic melanoma or NSCLC receiving ICI treatment?
Can we use FDG-PET to distinguish between early, not-yet-clinically-relevant tissue inflammation, thus early AE, and never-clinically-relevant tissue inflammation?
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