肺癌患者肌肉状况、营养风险、恶病质与化疗诱导毒性的关系

The association between skeletal muscle measures,nutritional risk,cachexia,and chemotherapy-induced toxicity in lung cancer patients

目的化疗是肺癌主要的治疗手段,然而化疗相关毒性发生率高,给患者带来不良体验并严重影响治疗方案和患者的生活质量。低骨骼肌重量、营养不良和恶病质与恶性肿瘤化疗毒性发生率较高有关。研究的主要目的是评估治疗基线身体成分、营养状况、恶病质与肺癌化疗毒性、剂量限制毒性(dose-limiting toxicity,DLT)之间的联系。方法这是一项对初次接受化疗肺癌患者的单中心前瞻性研究。通过多频生物电阻抗测量身体成分,计算骨骼肌指数(skeletal muscle index,SMI)来评估肌肉重量,使用握力和步速评估肌肉力量及功能,采用亚洲肌少症工作组2019标准评估是否存在肌肉衰减症。恶病质是根据肌肉重量和体重减轻来定义,而营养风险和营养不良分别是根据营养风险筛查2002和全球营养领导层诊断营养不良标准来评价。化疗毒性和DLT是根据不良事件通用标准术语来定义,并分为血液学、非血液学和DLT。通过单变量和多变量回归模型评估肌肉状况、营养状况和恶病质与毒性的关联。结果研究包含并分析126例患者,随访中位数为17.9个月(12~25个月)。在化疗期间,27.8%的患者经历了3/4级血液毒性,14.8%经历了任何≥2级非血液毒性,26.1%出现任何DLT。高龄、多种合并症是血液、非血液毒性和DLT的危险因素,肌肉力量和功能不足可增加血液毒性的发生[OR 1.121,95%CI 1.048~2.865,P=0.031],高SMI是DLT的保护性因素[OR 0.638,95%CI 0.242~0.083,P=0.021]。结论研究显示,在初治肺癌患者中,低SMI、低肌肉力量和功能的患者在化疗过程中出现DLT和3/4级血液毒性的风险增加,同时老年、多种合并症也是化疗毒性和DLT发生的危险因素。在临床工作中应进行评估,以发现化疗毒性的高危人群并进行预防。未来研究可考虑对不同肌肉状态进行化疗方案的调整。

Objective Chemotherapy is the main treatment for lung cancer.However,chemotherapy-related toxicity has a high incidence,which brings adverse experiences to patients and seriously affects treatment plans and quality of life.Low skeletal muscle mass(SMM),malnutrition,and cachexia are related to a higher incidence of chemotherapy toxicity in cancer patients.The main purpose of this study is to evaluate the relationship between baseline body composition,nutritional status,cachexia,and lung cancer chemotherapy toxicity and dose-limiting toxicity(DLT).Methods This is a single-center prospective study of lung cancer patients receiving chemotherapy for the first time.Body composition was measured using multi-frequency bioelectrical impedance,and the skeletal muscle index(SMI)was calculated.Grip strength and gait speed were used to assess muscle strength and function.The Asian Working Group on Sarcopenia(2019)criteria were used to evaluate the presence of sarcopenia.Cachexia was defined based on muscle mass and weight loss,while nutritional risk and malnutrition were evaluated based on the Nutritional Risk Screening 2002 and Global Leadership Initiative on Malnutrition criteria,respectively.Chemotherapy toxicity and DLT were defined according to the Common Terminology Criteria for Adverse Events and were divided into hematological,non-hematological,and DLT.The association between muscle condition,nutritional status,cachexia,and toxicity was evaluated by univariate and multivariate regression models.Results The study included and analyzed 126 patients,with a median follow-up of 17.9 months(12-25 months).During chemotherapy,27.8%of patients experienced grade 3/4 hematological toxicity,14.8%experienced any≥2 grade non-hematological toxicity,and 26.1%had any DLT.Old age and multiple comorbidities were risk factors for hematological,non-hematological toxicity,and DLT.Insufficient muscle strength and function could increase the incidence of hematological toxicity[OR 1.121,95%CI 1.048~2.865,P=0.031],and high SMI was a protective factor for DLT[OR 0.638,95%CI 0.242~0.083,P=0.021].Conclusions Lung patients with low SMI,low muscle strength and function have an increased risk of DLT and grade 3/4 hematological toxicity during chemotherapy.At the same time,elderly age and multiple comorbidities are also risk factors for chemotherapy toxicity and DLT.In clinical work,assessments should be conducted to identify high-risk populations for chemotherapy toxicity and preventive measures should be taken.Future research could consider adjusting chemotherapy plans based on different muscle statuses.