Abstract
Immune checkpoint inhibitors (ICIs) are now commonly used to treat patients with metastatic malignant melanoma. While concerns have been raised that the inflammatory response induced by ICIs may limit the ability of 18F-FDG PET/CT to assess tumor response, systematic analyses on the use of 18F-FDG PET/CT in this setting are mostly lacking. Thus, we set out to evaluate the association between tumor response on 18F-FDG PET/CT and prognosis in patients with metastatic malignant melanoma treated with ipilimumab. Methods: We analyzed 60 consecutive patients with metastatic melanoma who underwent 18F-FDG PET/CT scans at both pre- and post-treatment to evaluate treatment response after completion of ipilimumab therapy. Tumor response was assessed by the change in the sum of SULpeak of up to 5 lesions according to PET Response Criteria in Solid Tumors (PERCIST5). New lesions on PET that appeared suspicious for metastases were considered progressive metabolic disease (PMD). Because immunotherapy may cause new inflammatory lesions that are detectable on 18F-FDG PET/CT, we also evaluated an immunotherapy-modified response classification (imPERCIST5). In this classification, new lesions do not define PMD per se; rather, PMD requires an increase in the sum of SULpeak by 30%. We then investigated whether the response classification could be simplified by only measuring SULpeak for the lesion with the highest FDG uptake on the baseline or follow-up scan (imPERCIST1). The correlation between tumor response according to these three definitions and overall survival (OS) was evaluated and compared to known prognostic factors. Results: In responders and non-responders, the two-year OS was 57% vs. 29% for imPERCIST1 (P = 0.011), and 66% vs. 29% for imPERCIST5 (P = 0.003). After multivariate analysis, imPERCIST5 remained prognostic (HR 3.853; 95% CI 1.498-9.911; P = 0.005). New sites of focal FDG uptake occurred more often in patients with PMD (n = 24) by imPERCIST5 than in those with SMD (n = 7) or PMR (n = 4). In patients with PMR, two of four isolated new lesions regressed spontaneously during follow-up. Conclusion: In patients with metastatic melanoma treated with ipilimumab, tumor response according to PERCIST was associated with OS. Our data suggest that PMD should not be defined by the appearance of new lesions, but rather by an increase in the sum of SULpeak.
- Molecular Imaging
- Oncology: Melanoma
- PET/CT
- 18F-FDG
- Immune checkpoint inhibitor
- Ipilimumab
- Melanoma
- PERCIST
- Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.