FDG PET/CT for assessing tumour response to immunotherapy : Report on the EANM symposium on immune modulation and recent review of the literature

Abstract

This paper follows the immunotherapy symposium held during the European Association of Nuclear Medicine (EANM) 2017 Annual Congress. The biological basis of the immune checkpoint inhibitors and the drugs most frequently used for the treatment of solid tumours are reviewed. The issues of pseudoprogression (frequency, timeline), hyperprogression and immune-related side effects are discussed, as well as their implications for patient management. A review of the recent literature on the use of FDG PET for assessment of immunotherapy is presented, and recommendations are provided for assessing tumour response and reporting immune-related side effects with FDG PET based on published data and experts' experience. Representative clinical cases are also discussed.

Keywords: Hyperprogression; Immune checkpoint inhibitors; Immune-related side effects; Immunotherapy; Pseudoprogression; Therapy response.

Fig. 1

FDG PET images in a melanoma patient with breast and liver metastases treated with nivolumab after progression under anti-BRAF and anti-MEK treatment. a Baseline scan. b Early scan after two cycles shows progression in the breast and liver lesions as well as the appearance of bone metastases. c Scan after six cycles confirms the findings of progression. The case was classified as hyperprogression during immunotherapy (d)

Fig. 2

FDG PET images in a melanoma patient with lung metastases treated with nivolumab. a Baseline scan. b Early scan after two cycles shows two new lung lesions. c Scan after six cycles shows a complete metabolic response. Note the appearance of diffuse colonic uptake reported as possible colitis. The patient had no digestive symptoms. The progression seen after two cycles was considered to represent pseudoprogression

Fig. 3

PET/CT imaging in a patient with a previous complete metabolic response of subcutaneous metastases to immunotherapy. a, b Comparison of the baseline maximum intensity projection image (a) with the early posttreatment images (b) shows development of increased uptake in the pituitary fossa on the corresponding fused PET/CT image indicating hypophysitis and diffuse colonic uptake indicating colitis, which were confirmed biochemically and clinically. c Resolution of both complications is apparent after treatment with corticosteroids

Fig. 4

Serial maximum intensity projection images (a–c anterior, (d–f ) left lateral) show the development and resolution of pneumonitis. Note the dominance of parenchymal changes in the dependent lung, which is typical. There was a complete metabolic response with low-grade left hilar changes (c, f) consistent with reactive lymphadenopathy

Fig. 5

A patient with multiple melanoma metastases (nodes, diffuse bone involvement, multiple soft tissue lesions and solitary liver lesion) receiving nivolumab plus external beam radiation to the right axilla and a soft lesion near the left hip shows an almost complete metabolic response. Multiple signs of immune-related side effects are seen after two cycles of immunotherapy. Note the increased spleen uptake on the baseline scan due to an inflammatory syndrome

Fig. 6

A patient with new pulmonary metastases (a fused PET/CT image, c maximum intensity projection image). Following treatment with pembrolizumab (b fused PET/CT image, d maximum intensity projection image), dramatic uptake is seen in symmetrical hilar, mediastinal and portocaval nodes indicating treatment-induced sarcoidosis. Prior small pulmonary nodules have resolved