Rationale and Objectives
The purposes of this study were to provide a case-based overview of various immune-mediated side effects detected by 18F-Fluorodeoxyglucose (F-18 FDG) positron emission tomography-computed tomography (PET-CT) in the patients receiving ipilimumab immunotherapy for treatment of malignant melanoma, and discuss the importance of recognizing immune-mediated side effects in the use of F-18 FDG PET-CT for monitoring therapeutic effects of ipilimumab on metastatic melanoma.
Materials and Methods
This is a retrospective case series study of the patients diagnosed with melanoma who were subjected to immunomodulating therapy with ipilimumab. F-18 FDG PET-CT findings were reviewed, and the patients with immune-mediated side effects were selected for further analysis, in conjunction with review of clinical progress notes, the results of laboratory tests, and findings of other imaging tests.
Results
Four patients with immune-mediated side effects were identified among the patients being treated with ipilimumab and subjected to F-18 FDG PET-CT for monitoring therapeutic effects. These immune mediated side effects include new findings of abnormal increased FDG uptake associated with immune-mediated pancreatitis and hypophysitis, as well as immune-mediated thyroiditis and colitis reported previously.
Conclusions
Various immune-mediated side effects were detected by F-18 FDG PET-CT in the patients subjected to immunomodulating therapy with ipilimumab. It is essential for the interpreting provider to recognize and differentiate abnormal FDG uptake associated with immune-mediated side effects from hypermetabolic malignant lesions when using F-18 FDG PET-CT for monitoring therapeutic effects of ipilimumab on melanoma lesions.
Introduction
It is estimated by the American Cancer Society that melanoma of the skin will affect 76,100 patients in the United States in 2014 and will cause approximately 9710 deaths. In the male population of the United States, melanoma will be the fifth leading newly diagnosed type of cancer after prostate, lung and bronchus, colon and rectum, and urinary bladder. The lifetime risk of developing melanoma of the skin for men is estimated to be 1 in 34 (American Cancer Society).
Metastatic melanoma is commonly treated with systemic chemotherapeutic agents including, but not limited to, interferon alpha (IFNα), pegylated IFN, vemurafenib, High dose interleukin-2 (HD-IL2), dacarbazine, temozolomide, platinum compounds, and taxanes. A meta-analysis conducted in 2010 by Tarhini and Thalanayar on IFNα treatment showed 18% and 11% risk reduction for recurrence and death, respectively . However, there are many side effects of IFNα, including fatigue, fever, weight loss, thyroid dysfunction, reversible hepatic dysfunction, myelosuppression, and depression . High-dose IL-2 has been used in a subset of patients with Eastern Cooperative Oncology Group (ECOG) of 0 and excellent organ function, with progression-free survival of 8.9 months and median survival of 12 months for responders. However, the side effects can be severe and can include hypotension, arrhythmia, fever, chills, metabolic acidosis, neurotoxicity, nausea, dyspnea, oliguria, and rash . As a result, overall survival in patients receiving IL-2 has not been evaluated in randomized phase III trials .
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Materials and Methods
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Results
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Table 1
Immune-mediated Side Effects Detected by F-18 fluorodeoxyglucose (F-18 FDG) PET-CT
Side Effect FDG PET Findings CT Findings Pancreatitis Diffusely elevated pancreatic FDG uptake Loss of normal pancreatic lobulation Colitis Elevated FDG uptake involving the ascending colon Fluid-filled ascending colon with mild pericolonic stranding Hypophysitis Focally elevated uptake in the pituitary gland No correlative findings on localization CT Thyroiditis Bilateral elevated thyroid gland uptake No nodularity or CT findings
PET-CT, positron emission tomography-computed tomography.
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Case 1
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Case 2
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Case 3
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Case 4
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Discussion
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Acknowledgment
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