The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma

Show simple item record Daly, Louise E. Power, Derek G. O'Reilly, Aine Donnellan, Paul Cushen, Samantha J. O'Sullivan, Kathleen Twomey, Maria Woodlock, David P. Redmond, H. Paul Ryan, Aoife M. 2018-07-30T10:30:31Z 2018-07-30T10:30:31Z 2017
dc.identifier.citation Daly, L. E., Power, D. G., O'Reilly, Á., Donnellan, P., Cushen, S. J., O'Sullivan, K., Twomey, M., Woodlock, D. P., Redmond, H. P. and Ryan, A. M. (2017) 'The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma', British Journal of Cancer, 116, pp. 310- 317. doi: 10.1038/bjc.2016.431 en
dc.identifier.volume 116
dc.identifier.issued 3
dc.identifier.startpage 310
dc.identifier.endpage 317
dc.identifier.issn 0007-0920
dc.identifier.doi 10.1038/bjc.2016.431
dc.description.abstract Background: Body composition is an important predictor of drug toxicity and outcome. Ipilimumab (Ipi), a monoclonal antibody used to treat metastatic melanoma, has specific toxicities. No validated biomarkers that predict Ipi toxicity and efficacy exist. Also, the impact of Ipi on body composition has not been established. Methods: Patients with metastatic melanoma treated with Ipi between 2009 and 2015 were included. Body composition was assessed by computed tomography at baseline and after four cycles of Ipi. Sarcopenia and low muscle attenuation (MA) were defined using published cut-points. All adverse events (AEs) and immune-related AEs (irAEs) were recorded (Common Terminology Criteria For Adverse Event V.4.0). Results: Eighty-four patients were included in this study (62% male, median age 54 years). At baseline, 24% were sarcopenic and 33% had low MA. On multivariate analysis, sarcopenia and low MA were significantly associated with high-grade AEs (OR = 5.34, 95% CI: 1.15- 24.88, P = 0.033; OR = 5.23, 95% CI: 1.41-19.30, P = 0.013, respectively), and low MA was associated with high-grade irAEs (OR = 3.57, 95% CI: 1.09-11.77, P = 0.036). Longitudinal analysis (n = 59) revealed significant reductions in skeletal muscle area (SMA), total body fat-free mass, fat mass (all P<0.001) and MA (P = 0.030). Mean reduction in SMA was 3.3%/ 100 days (95% CI: - 4.48 to - 1.79%, P<0.001). A loss of SMA >= 7.5%/ 100 days (highest quartile) was a significant predictor of overall survival in multivariable Cox regression analysis (HR: 2.1, 95% CI: 1.02-4.56, P = 0.046). Conclusions: Patients with sarcopenia and low MA are more likely to experience severe treatment-related toxicity to Ipi. Loss of muscle during treatment was predictive of worse survival. Treatments to increase muscle mass and influence outcome warrant further investigation. en
dc.description.sponsorship Health Research Board (Clinical Research Facility, Cork (CRF-C)
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Nature Publishing Group en
dc.rights © 2017, Cancer Research UK. All rights reserved. This article is made available under a Creative Commons Attribution-NonCommercial-ShareAlike license. en
dc.subject Metastatic melanoma en
dc.subject Body composition en
dc.subject Sarcopenia en
dc.subject Muscle attenuation en
dc.subject Toxicity en
dc.subject Nutritional status en
dc.subject Ipilimumab en
dc.title The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Aoife Ryan, Food and Nutritional Sciences, University College Cork, Cork, Ireland.+353-21-490-3000. Email: en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.contributor.funder Science Foundation Ireland
dc.contributor.funder Health Research Board
dc.description.status Peer reviewed en
dc.identifier.journaltitle British Journal of Cancer en
dc.internal.IRISemailaddress en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/

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