PMID- 28072766
OWN - NLM
STAT- MEDLINE
DCOM- 20170608
LR  - 20181113
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 116
IP  - 3
DP  - 2017 Jan
TI  - The impact of body composition parameters on ipilimumab toxicity and survival in 
      patients with metastatic melanoma.
PG  - 310-317
LID - 10.1038/bjc.2016.431 [doi]
AB  - 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.
FAU - Daly, Louise E
AU  - Daly LE
AD  - School of Food and Nutritional Sciences/APC Microbiome Institute, University 
      College Cork, Cork, Ireland.
FAU - Power, Derek G
AU  - Power DG
AD  - Department of Medical Oncology, Cork University Hospital, Cork, Ireland.
FAU - O'Reilly, Aine
AU  - O'Reilly A
AD  - Department of Medical Oncology, University Hospital Galway, Galway, Ireland.
FAU - Donnellan, Paul
AU  - Donnellan P
AD  - Department of Medical Oncology, University Hospital Galway, Galway, Ireland.
FAU - Cushen, Samantha J
AU  - Cushen SJ
AD  - School of Food and Nutritional Sciences, University College Cork, Cork, Ireland.
FAU - O'Sullivan, Kathleen
AU  - O'Sullivan K
AD  - School of Mathematical Science, University College Cork, Cork, Ireland.
FAU - Twomey, Maria
AU  - Twomey M
AD  - Department of Radiology, Cork University Hospital, Cork, Ireland.
FAU - Woodlock, David P
AU  - Woodlock DP
AD  - Department of Radiology, University Hospital Galway, Galway, Ireland.
FAU - Redmond, Henry P
AU  - Redmond HP
AD  - Department of Surgery, Cork University Hospital and University College Cork, 
      Cork, Ireland.
FAU - Ryan, Aoife M
AU  - Ryan AM
AD  - School of Food and Nutritional Sciences, University College Cork, Cork, Ireland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170110
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Ipilimumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal/administration & dosage/*adverse effects
MH  - Body Composition/drug effects/*physiology
MH  - Female
MH  - Humans
MH  - Ipilimumab
MH  - Male
MH  - Melanoma/*drug therapy/*mortality/pathology
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Retrospective Studies
MH  - Sarcopenia/mortality
MH  - Skin Neoplasms/*drug therapy/*mortality/pathology
MH  - Survival Analysis
MH  - Young Adult
PMC - PMC5294486
COIS- The authors declare no conflict of interest.
EDAT- 2017/01/11 06:00
MHDA- 2017/06/09 06:00
PMCR- 2018/01/31
CRDT- 2017/01/11 06:00
PHST- 2016/08/23 00:00 [received]
PHST- 2016/10/28 00:00 [revised]
PHST- 2016/12/05 00:00 [accepted]
PHST- 2017/01/11 06:00 [pubmed]
PHST- 2017/06/09 06:00 [medline]
PHST- 2017/01/11 06:00 [entrez]
PHST- 2018/01/31 00:00 [pmc-release]
AID - bjc2016431 [pii]
AID - 10.1038/bjc.2016.431 [doi]
PST - ppublish
SO  - Br J Cancer. 2017 Jan;116(3):310-317. doi: 10.1038/bjc.2016.431. Epub 2017 Jan 
      10.