Body composition and checkpoint inhibitor treatment outcomes in advanced melanoma: a multicenter cohort study
ter Maat, L. S.; Van Duin, I. A. J.; Verheijden, R. J.; Moeskops, P.; Verhoeff, J. J. C.; Elias, S. G.; van Amsterdam, W. A. C.; Burgers, F. H.; Van den Berkmortel, F. W. P. J.; Boers-Sonderen, M. J.; Boomsma, M. F.; De Groot, J. W.; Haanen, J. B. A. G.; Hospers, G. A. P.; Piersma, D.; Vreugdenhil, G.; Westgeest, H. M.; Kapiteijn, E.; Labots, M.; Veldhuis, W. B. A. G.; Van Diest, P. J.; De Jong, P. A.; Pluim, J. P. W.; Leiner, T.; Veta, M.; Suijkerbuijk, K. P. M.
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IntroductionThe association of body composition with checkpoint inhibitor outcomes in melanoma is a matter of ongoing debate. In this study, we aim to add to previous evidence by investigating body mass index (BMI) alongside CT derived body composition metrics in the largest cohort to date. MethodPatients treated with first-line anti-PD1 {+/-} anti-CTLA4 for advanced melanoma were retrospectively identified from 11 melanoma reference centers in The Netherlands. Age, sex, Eastern Cooperative Oncology Group performance status, serum lactate dehydrogenase, presence of brain and liver metastases, number of affected organs and BMI at baseline were extracted from electronic patient files. From baseline CT scans, five body composition metrics were automatically extracted: skeletal muscle index, skeletal muscle density, skeletal muscle gauge, subcutaneous adipose tissue index and visceral adipose tissue index. All predictors were correlated in uni- and multivariable analysis to progression-free, overall and melanoma-specific survival (PFS, OS and MSS) using Cox proportional hazards models. ResultsA total of 1471 eligible patients were included. Median PFS and OS were 8.8 and 34.8 months, respectively. A significantly worse PFS was observed in underweight patients (multivariable HR=1.87, 95% CI 1.14-3.07). Furthermore, better OS was observed in patients with higher skeletal muscle density (multivariable HR=0.91, 95% CI 0.83-0.99) and gauge (multivariable HR=0.88, 95% CI 0.84-0.996), and a worse OS with higher visceral adipose tissue index (multivariable HR=1.13, 95% CI 1.04-1.22). No association with survival outcomes was found for overweightness or obesity and survival outcomes, or for subcutaneous adipose tissue. DiscussionOur findings suggest that underweight BMI is associated with worse PFS, whereas higher skeletal muscle density and lower visceral adipose tissue index were associated with better OS. These associations were independent of previously identified predictors, including sex, age, performance status and extent of disease. No significant association between higher BMI and survival outcomes was observed.
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