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晚期非小细胞肺癌患者的癌症恶病质、肌肉减少症及生化标志物——化疗毒性与预后价值

Cancer cachexia, sarcopenia and biochemical markers in patients with advanced non-small cell lung cancer-chemotherapy toxicity and prognostic value.

作者信息

Srdic Drazena, Plestina Sanja, Sverko-Peternac Ana, Nikolac Nora, Simundic Ana-Maria, Samarzija Miroslav

机构信息

Department for Respiratory Diseases "Jordanovac", University Hospital Centre Zagreb, Jordanovac 104, Zagreb, 10 000, Croatia.

Medical School University of Rijeka, Department for Respiratory Diseases "Jordanovac", University Hospital Centre Zagreb, Jordanovac 104, Zagreb, 10 000, Croatia.

出版信息

Support Care Cancer. 2016 Nov;24(11):4495-502. doi: 10.1007/s00520-016-3287-y. Epub 2016 May 28.

Abstract

PURPOSE

Cancer cachexia and sarcopenia are frequently observed in cancer patients and associated with poor survival. The majority of studies of cancer cachexia and sarcopenia have been done in patients with solid tumors of different origins, and there are currently no good predictors of the benefit of chemotherapy or factors that predict survival in advanced cancer. The purpose of our prospective study was to evaluate prevalence of cachexia and sarcopenia using international consensus definition and criteria for diagnosis in patients with diagnosed advanced non-small cell lung cancer (NSCLC) stage IIIB and IV and their relation to chemotherapy toxicity and survival prediction. A secondary aim was to compare several biochemical markers (CRP, IL-6, protein, and albumin) with time to tumor progression in order to assess prognostic value or to guide a treatment.

METHODS

Between December 2013 and April 2015, the prospective cohort study of 100 Caucasian patients with advanced NSCLC stage IIIB or IV, who were referred consecutively to Department for Respiratory Diseases "Jordanovac," was evaluated. Anthropometric measurements and biochemical data (CRP, albumin, protein, IL-6, haemoglobin) together with body composition measurements (total muscle cross-sectional area, lumbar skeletal muscle index) were obtained for each patient before starting with platinum-doublet therapy. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured by computerized tomography, and sarcopenia was defined using a previously published cutoff point. Toxicity was assessed after cycle 1 of treatment and time-to-tumor progression was determined prospectively.

RESULTS

One hundred patients with advanced lung cancer were recruited: 67 were male and median age was 64 years. The median time to disease progression was 187 days. The prevalence of cachexia and sarcopenia in study cohort was 69 and 47 %, respectively. CRP, IL-6, and albumin concentration in cachectic compared to non-cachectic patients demonstrated statistically significant difference (p = 0.020, p = 0.040, p = 0.003). Cachexia and sarcopenia were not found to be predictors of chemotoxicity nor was time to tumor progression. On the contrary, albumin concentration with established cutoff point of 37.5 g/L was clearly proved as the predictive factor of both chemotoxicity (OR (95 % CI) = 0.85; p < 0.001) and survival (HR (95 % CI) = 0.55).

CONCLUSIONS

Albumin level has been shown to be more important predictive marker of chemotherapy toxicity and survival than cachexia and sarcopenia are. This approach in clinical settings can be used to guide the choice of oncologic treatment.

摘要

目的

癌症恶病质和肌肉减少症在癌症患者中经常出现,且与生存率低相关。大多数关于癌症恶病质和肌肉减少症的研究是在不同来源的实体瘤患者中进行的,目前尚无化疗获益的良好预测指标或预测晚期癌症患者生存的因素。我们这项前瞻性研究的目的是使用国际共识定义和诊断标准,评估确诊的晚期非小细胞肺癌(NSCLC)ⅢB期和Ⅳ期患者中恶病质和肌肉减少症的患病率,以及它们与化疗毒性和生存预测的关系。次要目的是比较几种生化标志物(CRP、IL-6、蛋白质和白蛋白)与肿瘤进展时间,以评估预后价值或指导治疗。

方法

2013年12月至2015年4月期间,对100例连续转诊至“约尔达诺瓦茨”呼吸疾病科的晚期NSCLCⅢB期或Ⅳ期白种人患者进行了前瞻性队列研究。在开始铂类双联疗法之前,为每位患者获取人体测量数据和生化数据(CRP、白蛋白、蛋白质、IL-6、血红蛋白)以及身体成分测量数据(总肌肉横截面积、腰椎骨骼肌指数)。通过计算机断层扫描测量第三腰椎水平的骨骼肌横截面积,并使用先前公布的截断点定义肌肉减少症。在治疗第1周期后评估毒性,并前瞻性确定肿瘤进展时间。

结果

招募了100例晚期肺癌患者:67例为男性,中位年龄为64岁。疾病进展的中位时间为187天。研究队列中恶病质和肌肉减少症的患病率分别为69%和47%。与非恶病质患者相比,恶病质患者的CRP、IL-6和白蛋白浓度显示出统计学上的显著差异(p = 0.020,p = 0.040,p = 0.003)。未发现恶病质和肌肉减少症是化学毒性的预测指标,也不是肿瘤进展时间的预测指标。相反,白蛋白浓度以37.5 g/L的既定截断点被明确证明是化学毒性(OR(95%CI)= 0.85;p < 0.001)和生存(HR(95%CI)= 0.55)的预测因素。

结论

白蛋白水平已被证明是比恶病质和肌肉减少症更重要的化疗毒性和生存预测标志物。这种方法在临床环境中可用于指导肿瘤治疗的选择。

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