Background
Body composition is minimally investigated in an immunotherapy era. Specific body composition signals such as myosteatosis may reflect aspects of patients' immunology and thereby their ability to respond to immunotherapies. Ipilimumab is a key checkpoint inhibitor in metastatic melanoma. As an antibody, it may also be more accurately dosed using body composition parameters rather than weight alone. This retrospective study aimed to investigate body composition‐based dosing and outcomes.
Methods
Pretreatment computed tomography images from metastatic melanoma, ipilimumab‐treated patients from 2009 to 2014 were used to measure myosteatosis [skeletal muscle radiographic density or SMD, in Hounsfield units (HU)] and surface area (cm2) as previously described. Cut point analysis determined whether a level of ipilimumab dose and myosteatosis demonstrated differences in progression‐free (PFS) and overall survival (OS). Secondary endpoints included objective response rates and toxicities.
Results
Of 121 identified, 97 patients were evaluable. Baseline demographics included 56 years median age, 60% male participants, and 23.7% with BRAF mutations. SMD analysis identified cut‐offs of SMD < 42 in those with BMI < 25 kg/m2 and <20 HU in those with BMI ≥ 25 kg/m2, respectively. Low SMD patients had poorer median PFS [2.4 vs. 2.7 months, hazard ratio (HR) 1.76, P = 0.008] and OS (5.4 vs. 17.5 months, HR 2.47, P = 0.001), which remained significant in multivariate modelling. High SMD patients had more immune‐related adverse events, better objective response rates (17.9 vs. 3.3%, P = 0.051), and lower baseline neutrophil‐to‐lymphocyte ratio (21 vs. 39%, P = 0.049). Separately, patients receiving <2.03 mg/cm2 had improved median PFS (3.0 vs. 2.6 months, HR 1.88, P = 0.02) and OS (14.9 vs. 5.7 months, HR 1.98, P = 0.01).
Conclusions
Low SMD and receiving >2.03 mg/cm2 are prognostic of poorer melanoma outcomes post ipilimumab. SMD may identify patients with flawed immunology and predict who may better respond to such therapy. Ipilimumab dosing by skeletal muscle index stands in contrast to weight‐based dosing and may demonstrate a more accurate method of antibody dosing.
A novel "dissolution-capture" method for the fabrication of nitrogen-doped hollow mesoporous spherical carbon capsules (N-HMSCCs) with high capability for supercapacitor is developed. The fabrication process is performed by depositing mesoporous silica on the surface of the polyacrylonitrile nanospheres, followed by a dissolution-capture process occurring in the polyacrylonitrile core and silica shell. The polyacrylonitrile core is dissolved by dimethylformamide treatment to form a hollow cavity. Then, the polyacrylonitrile is captured into the mesochannel of silica. After carbonization and etching of silica, N-HMSCCs with uniform mesopore size are produced. The N-HMSCCs show a high specific capacitance of 206.0 F g(-1) at a current density of 1 A g(-1) in 6.0 M KOH due to its unique hollow nanostructure, high surface area, and nitrogen content. In addition, 92.3% of the capacitance of N-HMSCCs still remains after 3000 cycles at 5 A g(-1). The "dissolution-capture" method should give a useful enlightenment for the design of electrode materials for supercapacitor.
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