Imaging Features of Toxicities by Immune Checkpoint Inhibitors in Cancer Therapy

Abstract

Purpose of review: With 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 findings: Important 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.

Summary: Early 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.

Keywords: Imaging; Immune checkpoint inhibitors; Immune-related adverse events.

Fig. 1

72-year-old man with colitis grade 2 after 4th dose of ipilimumab. a Normal colon before ipilimumab. b Colitis with diffuse colitis pattern. Colonic wall thickening and mucosal hyperenhancement (arrows). c Improvement after ipilimumab interruption and glucocorticoids

Fig. 2

33-year-old man with hepatitis grade 3 after 3rd dose of nivolumab plus ipilimumab. a Normal sized liver before combination therapy. b Hepatis with convex shaped hepatomegaly (arrows) and periportal lymphadenopathy (dotted arrow)

Fig. 3

54-year-old man with pancreatitis after 1st dose of pembrolizumab. a Normal pancreas before pembrolizumab. b Pancreatitis with pancreatic enlargement and fat stranding (arrows)

Fig. 4

73-year-old man with pneumonitis grade 3 after 3rd dose of ipilimumab given sequentially after 9 doses of pembrolizumab due to disease progression. a and b Pneumonitis with cryptogenic organizing pneumonia pattern. Mixed and multifocal peripheral ground glass opacities and consolidations. c and d Improvement after ipilimumab interruption and glucocorticoids. Arrows show multiple lung metastases

Fig. 5

73-year-old man with hypophysitits grade 3 after 5th dose of ipilimumab. a Normal pituitary gland before ipilimumab. b Hypophysitis with moderate enlargement of the pituitary and homogeneous contrast enhancement (arrow). c Recovery of pituitary gland to normal size after ipilimumab interruption and glucocorticoids. Dotted arrow shows brain metastasis with partial regression

Fig. 6

76-year-old man with arthritis after 21st dose of nivolumab. a PET-CT shows oligoarthritis with increased FDG uptake in the shoulders, elbows and wrists (arrows). b Shoulder arthritis with thickened synovial and increased vascularity. c Metacarpophalangeal arthritis with thickened increased vascularized synovia

Fig. 7

67-year-old woman with sarcoid lymphadenopathy after 9th dose of pembrolizumab. a Normal mediastinal and hilar lymph nodes before pembrolizumab. b Sarcoid lymphadenopathy (biopsy confirmed) with symmetric hilar and mediastinal enlargement of lymph nodes