Imaging Features of Toxicities by Immune Checkpoint Inhibitors in Cancer Therapy

Abstract

Purpose of reviewWith the increasing use of immune checkpoint inhibitors in cancer therapy radiographic profiling of frequent and serious immune-related adverse events (irAEs) becomes more relevant. This article reviews imaging features of irAEs induced by the anti-CTLA-4 and anti-PD-1 antibodies ipilimumab, nivolumab and pembrolizumab.Recent findingsImportant radiological manifestations are immune-related colitis, hepatitis, pancreatitis, hypophysitis, pneumonitis, arthritis and sarcoid-like lymphadenopathy. Typical imaging features are summarized and compared with other relevant differential diagnoses.SummaryEarly diagnosis and appropriate therapeutic decisions are required for a successful treatment of irAEs. In addition to staging and follow-up imaging, identification and monitoring of adverse events becomes an important radiologic aspect in oncologic care.

Nivolumab Induced Seronegative Arthritis in a Patient With Refractory Hodgkin’s Lymphoma

“…Severe IRAEs like colitis, pneumonitis or hepatitis are rare but they can be life-threatening. 5,6 The incidence of musculoskeletal IRAEs has not been clarified yet and may be higher than shown in the literature. Different cases diagnosed with arthralgia, polymyalgia rheumatica, psoriatic arthritis, rheumatoid arthritis, myositis, myopathy, sarcoidosis, sicca syndrome, and systemic lupus erythematosus following nivolumab therapy were reported in the literature.…”

“…3,4 The percentage of IRAEs with nivolumab was reported to be 10-15%. 5 Skin manifestations and elevated transaminases can be seen at an approximate rate of 30%. Severe IRAEs like colitis, pneumonitis or hepatitis are rare but they can be life-threatening.…”

Imaging of Adverse Events Related to Checkpoint Inhibitor Therapy

“…Crohn's disease affects mainly terminal ileum with a patchy transmural distribution while ulcerative colitis increases intensity distally. Infectious colitis is most commonly localized in the right colon and is characterized by wall thickening with homogeneous enhancement while pseudomembranous colitis normally appears with marked circumferential or eccentric wall thickening [43]. Occasionally, the diagnosis of irAEs-related colitis is supported with biopsy which may show neutrophilic infiltrate, lymphocytic infiltrate, or a mix of both [44].…”

“…US may show prominent periportal echogenicity and gallbladder wall edema (Figure 4) [47]. Differential diagnosis should be made with viral hepatitis, alcoholic liver disease, and idiopathic autoimmune hepatitis [43]. Therefore, in case of a diagnostic doubt viral serology, history of alcohol abuse, steatohepatitis, cirrhosis, and the presence of autoantibodies should be evaluated.…”

“…An example of pembrolizumab-induced pneumonitis with an AIP pattern is shown in Figure 5. Clinical history may help to rule out pneumonitis with different etiology as other drug-induced pneumonitis, radiation pneumonitis, and bacterial pneumonia [43]. Radiation pneumonitis usually involves an area of the lung that is exposed to at least 30-40 Gray; in addition, such pneumonitis is not limited by interlobar fissures or by broncho-vascular structures and is characterized by ground glass opacities which may increase in density over time [62].…”