Postdiagnosis Loss of Skeletal Muscle, but Not Adipose Tissue, Is Associated with Shorter Survival of Patients with Advanced Pancreatic Cancer
Postdiagnosis Loss of Skeletal Muscle, but Not Adipose Tissue, Is Associated with Shorter Survival of Patients with Advanced Pancreatic Cancer
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DOI：
10.1158/1055-9965.epi-19-0370
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发表时间：
2019-12-01
影响因子：
3.8
通讯作者：
Wolpin, Brian M.
中科院分区：
文献类型：
--
作者：
Babic, Ana;Rosenthal, Michael H.;Wolpin, Brian M.
背景：胰腺癌与恶病质的发展有关，恶病质是一种被认为限制生存的消耗综合征。很少有研究纵向量化外周组织或确定预测未来组织浪费的生物标志物。方法：对164例晚期胰腺癌患者在诊断时及50 ~ 120天后的脂肪和肌肉组织进行了CT测量。采用Cox比例风险回归评估组织变化和生存率。循环标志物的基线水平与未来组织损耗的关系进行了检查。结果：与每30天肌肉变化最低四分位数（平均增加0.8 +/- 2.0 cm(2)）的患者相比，最高四分位数（平均减少12.9 +/- 4.9 cm(2)）的患者死亡风险比（HR）为2.01[95%可信区间（CI）， 1.12-3.62]。肌肉衰减变化最高四分位数的患者（平均减少4.9 +/- 2.4 Hounsfield单位）与最低四分位数的患者（平均增加2.4 +/- 1.6 Hounsfield单位）相比，anhr为2.19 （95% CI, 1.18-4.04）。脂肪组织的变化与存活无关。诊断时较高的血浆支链氨基酸（BCAA, P = 0.004）和较低的单核细胞化学引诱蛋白-1 （MCP-1, P = 0.005）与未来更大的肌肉损失相关。结论：在晚期胰腺癌患者中，诊断后2至4个月的肌肉损失和肌肉密度降低与生存率降低相关。诊断时BCAAs和mcp -1水平与随后的肌肉损失相关。影响：诊断时的BCAAs和mcp -1水平可以确定未来组织浪费的高危人群。
Background: Pancreatic cancer is associated with development of cachexia, a wasting syndrome thought to limit survival. Fewstudies have longitudinally quantified peripheral tissues or identified biomarkers predictive of future tissue wasting.Methods: Adipose and muscle tissue were measured by computed tomography (CT) at diagnosis and 50 to 120 days later in 164 patients with advanced pancreatic cancer. Tissue changes and survival were evaluated by Cox proportional hazards regression. Baseline levels of circulating markers were examined in relation to future tissue wasting.Results: Compared with patients in the bottom quartile of muscle change per 30 days (average gain of 0.8 +/- 2.0 cm(2)), those in the top quartile (average loss of 12.9 +/- 4.9 cm(2)) had a hazard ratio (HR) for death of 2.01 [95% confidence interval (CI), 1.12-3.62]. Patients in the top quartile of muscle attenuation change (average decrease of 4.9 +/- 2.4 Hounsfield units) had anHRof 2.19 (95% CI, 1.18-4.04) compared with those in the bottom quartile (average increase of 2.4 +/- 1.6 Hounsfield units). Changes in adipose tissue were not associated with survival. Higher plasma branched chain amino acids (BCAA; P = 0.004) and lower monocyte chemoattractant protein-1 (MCP-1; P = 0.005) at diagnosis were associated with greater future muscle loss.Conclusions: In patients with advanced pancreatic cancer, muscle loss and decrease in muscle density in 2 to 4 months after diagnosis were associated with reduced survival. BCAAs andMCP-1 levels at diagnosis were associated with subsequent muscle loss.Impact: BCAAs andMCP-1 levels at diagnosis could identify a high-risk group for future tissue wasting.