Abstract
BackgroundIn patients with metastatic melanoma and KIT amplifications and/or mutations, therapy with imatinib mesylate may prolong survival. 18F-labeled 2-fluoro-2-deoxy-D-glucose (18F-FDG) PET/CT may be used to assess metabolic response. We investigated associations of metabolic response, mutational status, progression-free survival and overall survival in this population.MethodsBaseline and 4-week follow-up 18F-FDG-PET/CT were evaluated in 17 patients with metastatic melanoma and KIT amplifications and/or mutations treated with imatinib in a multicenter phase II clinical trial. The maximum standardized uptake values (SUVmax) were measured in up to 10 lesions on each scan. Metabolic response was classified using modified EORTC criteria. Each patient had a diagnostic CT or MR at baseline, after 6 weeks of therapy and then at intervals of 2 months and anatomic response was classified using RECIST 1.0. Median follow-up was 9.8 months.ResultsPartial metabolic response (PMR), stable metabolic disease (SMD) and progressive metabolic disease (PMD) was seen in 5 (29%), 5 (29%), and 7 (41%) patients respectively. Five patients (29%) had a KIT mutation in exon 11, four of whom (80%) had PMR while 1 (20%) had SMD. Twelve patients (71%) did not have a KIT mutation in exon 11, and only 1 (8%) had PMR, 4 (33%) had SMD and 7 (58%) had PMD. There was agreement of metabolic and anatomic classification in 12 of 17 patients (71%). Four of 17 patients (24%) had PR on both metabolic and anatomic imaging and all had a KIT mutation in exon 11. Survival of patients with PMD was lower than with SMD or PMR.ConclusionsMetabolic response by 18F-FDG-PET/CT is associated with mutational status in metastatic melanoma patients treated with imatinib. 18F-FDG-PET/CT may be a predictor of outcome, although a larger study is needed to verify this.Clinical trial registrationNCT00424515
Highlights
In patients with metastatic melanoma and KIT amplifications and/or mutations, therapy with imatinib mesylate may prolong survival. 18F-labeled 2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) may be used to assess metabolic response
Our aim was to assess the metabolic response of patients with metastatic melanoma and a KIT mutation and/or amplification treated with imatinib using 18F-FDG-PET/CT and to investigate the association of 18F-FDG uptake with mutational status, time-to-progression (TTP) and overall survival (OS)
Study description The institutional review boards of the sites participating in a phase II multicenter clinical trial of imatinib in metastatic melanoma with KIT amplifications and/or mutations approved the study before patient enrollment and continuing approval was maintained throughout the study (This clinical trial was approved by the DanaFarber/Harvard Cancer Center IRB)
Summary
In patients with metastatic melanoma and KIT amplifications and/or mutations, therapy with imatinib mesylate may prolong survival. 18F-labeled 2-fluoro-2-deoxy-D-glucose (18F-FDG) PET/CT may be used to assess metabolic response. Mucosal and acral melanoma arising from sites such as the palms, soles and nail beds as well as cutaneous melanoma arising from chronically sun-damaged skin are forms of the disease with different but overlapping oncogenes and biologic behavior [1,2,3,4,5] that have recently been found to harbor KIT mutations [6,7,8,9,10] The majority of these mutations occur in exon 11 at the juxtamembrane portion of the protein, which predicts responsiveness to imatinib mesylate [11]. Imaging in patients with GIST often includes 18F-labeled 2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT), which can show metabolically active disease and may be more effective for evaluating therapeutic response to tyrosine kinase inhibition than anatomic imaging [16,17,18,19,20].
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