Imaging assessment of toxicity related to immune checkpoint inhibitors

Abstract

In recent years, a wide range of cancer immunotherapies have been developed and have become increasingly important in cancer treatment across multiple oncologic diseases. In particular, immune checkpoint inhibitors (ICIs) offer promising options to improve patient outcomes. However, a major limitation of these treatments consists in the development of immune-related adverse events (irAEs) occurring in potentially any organ system and affecting up to 76% of the patients. The most frequent toxicities involve the skin, gastrointestinal tract, and endocrine system. Although mostly manageable, potentially life-threatening events, particularly due to neuro-, cardiac, and pulmonary toxicity, occur in up to 30% and 55% of the patients treated with ICI-monotherapy or -combination therapy, respectively. Imaging, in particular computed tomography (CT), magnetic resonance imaging (MRI), and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT), plays an important role in the detection and characterization of these irAEs. In some patients, irAEs can even be detected on imaging before the onset of clinical symptoms. In this context, it is particularly important to distinguish irAEs from true disease progression and specific immunotherapy related response patterns, such as pseudoprogression. In addition, there are irAEs which might be easily confused with other pathologies such as infection or metastasis. However, many imaging findings, such as in immune-related pneumonitis, are nonspecific. Thus, accurate diagnosis may be delayed underling the importance for adequate imaging features characterization in the appropriate clinical setting in order to provide timely and efficient patient management. 18F-FDG-PET/CT and radiomics have demonstrated to reliably detect these toxicities and potentially have predictive value for identifying patients at risk of developing irAEs. The purpose of this article is to provide a review of the main immunotherapy-related toxicities and discuss their characteristics on imaging.

Is 18F-FDG-PET/CT an Optimal Imaging Modality for Detecting Immune-Related Adverse Events after Immune-Checkpoint Inhibitor Therapy? Pros and Cons

“…A few studies linked the high splenic-to-liver ratio on PET/CT to splenic irAEs, notably with ipilimumab in metastatic melanoma [7,71,72]. However, splenic irAEs are relatively rare, and splenic uptake is more often regarded as a surrogate of immune On some rare occasions, adrenalitis occurs as an irAE; on PET, it is mainly seen as increased FDG uptake; when turning into a chronic phase, it may be seen as bilateral atrophy of the glands [69].…”

“…Pneumonitis is a rare but sometimes lethal irAE following ICIs. It is even the most lethal irAE with anti-PD-1/PD-L1 drugs, being the cause of ~35% of immunotherapyrelated deaths (~1% of deaths by CTLA-4 inhibitors), making it sometimes necessary to discontinue treatment [7,29,79,80]. Nishino et al (2016) found that the median onset time of pneumonitis was 2.6 months after immunotherapy initiation [81].…”

“…18 F-FDG PET/MRI (a hybrid imaging modality combining FDG PET with MRI) offers comprehensive myocardial assessment, valuable when biopsies are risky or other tests are inconclusive. Alternative PET tracers such as 68 Ga-DOTATOC show promise for early detection of ICI-myocarditis, correlating with serum cardiac troponin I and immune markers, such as cytokines and chemokines [7].…”

“…Challenges in Differentiation-It can be difficult to distinguish between signs of irAEs and tumor progression or other non-cancerous conditions, potentially leading to diagnostic ambiguity [7].…”

Cancer Immunotherapy and Medical Imaging Research Trends from 2003 to 2023: A Bibliometric Analysis

“…Currently, the efficacy and adverse events of tumor immunotherapy can be preliminarily assessed through imaging studies. [9][10][11] It is also possible to establish image-based biomarkers 12,13 or efficacy prediction models combined with clinical characteristics to screen the appropriate population for immunotherapy and implement personalized treatment. 14,15 Clinically, it is routine to use various medical image-based efficacy evaluation standards for solid tumors to assess treatment efficacy.…”