Pitfalls in the radiological response assessment of immunotherapy

Abstract

Immunotherapies comprise of a class of cancer therapies that are increasingly used for treatment of several cancer entities. Active immunotherapies encompassing immune checkpoint inhibitors are the most widespread class of immunotherapies, with indications for melanoma, non-small lung cancer, renal cell carcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, and Hodgkin's lymphoma. Immune checkpoint inhibitors have demonstrated unique response patterns that are not adequately captured by traditional response criteria such das the Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization criteria. Consequently, adaptions of these criteria have been released such as the immune-related RECIST and immune RECIST, which account for the specialities of immunotherapies. Immunotherapies can cause a distinct set of adverse events such as pneumonitis, colitis, and hypophysitis. In addition, atypical treatment response patterns termed pseudoprogression have been observed. Thereby, new or enlarging lesions appear after treatment start and mimic tumor progression, which is followed by an eventual decrease in total tumor burden. In this review article we will describe pitfalls in the radiological response assessment of immunotherapies, focusing on pseudoprogression and imaging appearances of common immune-related adverse events.

Keywords: Hyperprogression; Immune checkpoint inhibitor; PD-1 inhibitor; Pneumonitis; Pseudoprogression.

Fig. 1

Pseudoprogression in 54-year-old man with non-small cell lung cancer receiving immune checkpoint inhibitor therapy. a Coronary fluorodeoxyglucose positron emission tomopraphy/computed tomography (¹⁸F-FDG-PET/CT) imaging obtained before therapy demonstrate ¹⁸F-FDG avid malignant tumor in the right lung. b 5 weeks after treatment initiation tumor size and FDG uptake increased. Therapy was continued and 6 weeks thereafter tumor size shrinkage and a reduced ¹⁸F-FDG uptake were observed (c)

Fig. 2

Organizing pneumonia in a 53-year-old man with epithelial cell carcinoma showing patchy opacities in both lungs and sparing of the subpleural space

Fig. 3

Sarcoid-like reaction in a 77-year-old man with non-small cell lung cancer receiving immune checkpoint inhibitor therapy. a, b Axial fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) image obtained before therapy demonstrate a malignant right pleural effusion. c, d 4 weeks after treatment initiation, numerous intrapulmonary micronodules were detectable in both lungs, predominately right-sided. In addition, enlarged hilar/mediastinal lymph nodes with increased ¹⁸F-FDG newly developed, consistent with a sarcoid-like reaction. In contrast, malignant tumor burden resolved completely