Mapping heterogeneity in glucose uptake in metastatic melanoma using quantitative F-18-FDG PET/CT analysis

BackgroundMetastatic melanoma patients can have durable responses to systemic therapy and even long-term survival. However, a large subgroup of patients does not benefit. Tumour metabolic alterations may well be involved in the efficacy of both targeted and immunotherapy. Knowledge on in vivo tumour glucose uptake and its heterogeneity in metastatic melanoma may aid in upfront patient selection for novel (concomitant) metabolically targeted therapies. The aim of this retrospective study was to provide insight into quantitative F-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-18-FDG PET/CT) parameters and corresponding intra- and inter-patient heterogeneity in tumour F-18-FDG uptake among metastatic melanoma patients. Consecutive, newly diagnosed stage IV melanoma patients with a baseline F-18-FDG PET/CT scan performed between May 2014 and December 2015 and scheduled to start first-line systemic treatment were included. Volume of interests (VOIs) of all visible tumour lesions were delineated using a gradient-based contour method, and standardized uptake values (SUVs), metabolically active tumour volume (MATV) and total lesion glycolysis (TLG) were determined on a per-lesion and per-patient basis. Differences in quantitative PET parameters were explored between patient categories stratified by BRAF(V600) and RAS mutational status, baseline serum lactate dehydrogenase (LDH) levels and tumour programmed death-ligand 1 (PD-L1) expression.ResultsIn 64 patients, 1143 lesions 1ml were delineated. Median number of lesions 1ml was 6 (range 0-168), median maximum SUVpeak 9.5 (range 0-58), median total MATV 29ml (range 0-2212) and median total TLG 209 (range 0-16,740). Per-patient analysis revealed considerable intra- and inter-patient heterogeneity. Maximum SUVs, MATV, number of lesions and TLG per patient did not differ when stratifying between BRAF(V600) or RAS mutational status or PD-L1 expression status, but were higher in the patient group with elevated LDH levels (>250U/l) compared to the group with normal LDH levels (P