Quantitative imaging biomarkers of immune-related adverse events in immune-checkpoint blockade-treated metastatic melanoma patients: a pilot study

Abstract

Purpose To develop quantitative molecular imaging biomarkers of immune-related adverse event (irAE) development in malignant melanoma (MM) patients receiving immune-checkpoint inhibitors (ICI) imaged with 18F-FDG PET/CT. Methods 18F-FDG PET/CT images of 58 MM patients treated with anti-PD-1 or anti-CTLA-4 ICI were retrospectively analyzed for indication of irAE. Three target organs, most commonly affected by irAE, were considered: bowel, lung, and thyroid. Patient charts were reviewed to identify which patients experienced irAE, irAE grade, and time to irAE diagnosis. Target organs were segmented using a convolutional neural network (CNN), and novel quantitative imaging biomarkers — SUV percentiles (SUVX%) of 18F-FDG uptake within the target organs — were correlated with the clinical irAE status. Area under the receiver-operating characteristic curve (AUROC) was used to quantify irAE detection performance. Patients who did not experience irAE were used to establish normal ranges for target organ 18F-FDG uptake. Results A total of 31% (18/58) patients experienced irAE in the three target organs: bowel (n=6), lung (n=5), and thyroid (n=9). Optimal percentiles for identifying irAE were bowel (SUV95%, AUROC=0.79), lung (SUV95%, AUROC=0.98), and thyroid (SUV75%, AUROC=0.88). Optimal cut-offs for irAE detection were bowel (SUV95%>2.7 g/mL), lung (SUV95%>1.7 g/mL), and thyroid (SUV75%>2.1 g/mL). Normal ranges (95% confidence interval) for the SUV percentiles in patients without irAE were bowel [1.74, 2.86 g/mL], lung [0.73, 1.46 g/mL], and thyroid [0.86, 1.99 g/mL]. Conclusions Increased 18F-FDG uptake within irAE-affected organs provides predictive information about the development of irAE in MM patients receiving ICI and represents a potential quantitative imaging biomarker for irAE. Some irAE can be detected on 18F-FDG PET/CT well before clinical symptoms appear.

Challenges and opportunities for implementing hypofractionated radiotherapy in Africa: lessons from the HypoAfrica clinical trial

“…For patient recruitment, the inclusion criteria outlined in the study protocol facilitated the selection of patients at each study site that matched the target population. To homogenise data collection, we introduced a centralised platform with data collected in a relational database within the existing Networks of Imaging eXcellence (NIX) infrastructure, used in other multi-centre studies [ 25 ]. NIX allows homogenisation of the processes for acquisition and collation of patient imaging and other clinical data and provides a legal, ethical and logistic framework for linking geographically, politically and functionally disparate data sets with each other, and provides an environment for cross-validation of derived biomarkers and models.…”

Positron emission tomography molecular imaging to monitor anti-tumor systemic response for immune checkpoint inhibitor therapy

“…On FDG PET/CT, irAEs are characterized by increased uptake of FDG in the affected organ, and subsequent reduction in uptake indicates remission of acute inflammation, meaning that it can be radiographically manifested to a certain extent [101]. Therefore, 18 F-FDG PET/CT is a sensitive method for recognizing inflammatory processes that can be reflective of irAEs (Table 3) [102].…”

“…The optimal percentiles for identifying irAEs were as follows: intestinal (SUV: 95%), lungs (SUV: 95%), and thyroid (SUV: 75%). This study provides more accurate PET-based prediction information for the occurrence of irAEs in melanoma patients treated with ICIs [102]. The introduction of artificial intelligence (AI) analysis methods provides quantitative and high-throughput information for PET imaging to effectively detect irAEs.…”

PET/CT molecular imaging in the era of immune-checkpoint inhibitors therapy

“…However, the utility of 18 F-FDG PET/CT imaging in irAEs screening and monitoring is largely under-recognized currently (2). 18 F-FDG PET/CT imaging may be a sensitive method to identify the development and severity of irAEs, which usually present as a new non-neoplastic lesion with increased FDG accumulation after ICI treatment (56). For instance, elevated thyroid SUVmax commonly suggests ICI-related thyroiditis (57), while a diffuse increase of FDG uptake in the pancreas is a characteristic manifestation of ICI-related pancreatitis (58).…”

“…A study on patients with metastatic melanoma treated with ICIs found that novel quantitative imaging biomarkers, i.e. the SUV percentiles (SUV X% ) of 18 F-FDG uptake within the target organs, could be predictive of irAEs in the bowel, stomach, and thyroid ( 56 ). This study also demonstrated that some irAEs could be detected on 18 F-FDG PET/CT imaging before the onset of clinical symptoms, which showed increased 18 F-FDG uptake in the affected organs.…”