Nattenmüller Johanna, Wochner Raoul, Muley Thomas, Steins Martin, Hummler Simone, Teucher Birgit, Wiskemann Joachim, Kauczor Hans-Ulrich, Wielpütz Mark Oliver, Heussel Claus Peter
Department of Diagnostic and Interventional Radiology, University Hospital, Im Neuenheimer Feld, Heidelberg, Germany.
Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld, Heidelberg, Germany.
PLoS One. 2017 Jan 20;12(1):e0169136. doi: 10.1371/journal.pone.0169136. eCollection 2017.
Cachexia and sarcopenia are associated with poor outcome and increased chemotherapy-induced toxicity in lung cancer patients. However, the complex interplay of obesity, sarcopenia and cachexia, and its impact on survival in the context of first-line-chemotherapy is not yet understood.
In 200 consecutively recruited lung cancer patients (70 female, mean age 62y; mean BMI 25 kg/m2; median follow-up 15.97 months) with routine staging-CT before and after chemotherapy (CTX, mean interval: 4.3 months), densitometric quantification of total (TFA), visceral (VFA), and subcutaneous-fat-area (SFA), inter-muscular-fat-area (IMFA), muscle-density (MD), muscle-area (MA) and skeletal-muscle-index (SMI) was performed retrospectively to evaluate changes under chemotherapy and the impact on survival.
We observed increases in TFA, VFA, SFA, VFA/SFA, and IMFA (p<0.05-0.001), while there were decreases in MA, MD and BMI (p<0.05-0.001) after chemotherapy. High pre-therapeutic VFA/SFA was a predictive factor for poor survival (HR = 1.272; p = 0.008), high pre-therapeutic MD for improved survival (HR = 0.93; p<0.05). Decrease in BMI (HR = 1.303; p<0.001), weight (HR = 1.067; p<0.001) and SMI (HR = 1.063; p<0.001) after chemotherapy were associated with poor survival. Patients with ≥4 CTX-cycles showed increased survival (17.6 vs. 9.1months), less muscle depletion (SMIdifference: p<0.05) and no BMI loss (BMIdifference: p<0.001).
After chemotherapy, patients exhibited sarcopenia with decreased muscle and increased adipose tissue compartments, which was not adequately mirrored by BMI and weight loss but by imaging. Particularly sarcopenic patients received less CTX-cycles and had poorer survival. As loss of BMI, weight and muscle were associated with poor survival, early detection (via imaging) and prevention (via physical exercise and nutrition) of sarcopenia may potentially improve outcome and reduce chemotherapy-induced toxicity.
恶病质和肌肉减少症与肺癌患者的不良预后及化疗诱导的毒性增加有关。然而，肥胖、肌肉减少症和恶病质之间复杂的相互作用及其在一线化疗背景下对生存的影响尚不清楚。
对200例连续招募的肺癌患者（70例女性，平均年龄62岁；平均体重指数25kg/m²；中位随访时间15.97个月）进行回顾性研究，这些患者在化疗前后（化疗，平均间隔时间：4.3个月）均进行了常规分期CT检查，通过密度测定法对总脂肪面积（TFA）、内脏脂肪面积（VFA）、皮下脂肪面积（SFA）、肌间脂肪面积（IMFA）、肌肉密度（MD）、肌肉面积（MA）和骨骼肌指数（SMI）进行量化，以评估化疗期间的变化及其对生存的影响。
我们观察到化疗后TFA、VFA、SFA、VFA/SFA和IMFA增加（p<0.05 - 0.001），而MA、MD和体重指数下降（p<0.05 - 0.001）。治疗前高VFA/SFA是生存不良的预测因素（风险比=1.272；p = 0.008），治疗前高MD则提示生存改善（风险比=0.93；p<0.05）。化疗后体重指数下降（风险比=1.303；p<0.001）、体重下降（风险比=1.067；p<0.001）和SMI下降（风险比=1.063；p<0.001）与生存不良相关。接受≥4个化疗周期的患者生存期延长（17.6个月对9.1个月），肌肉消耗减少（SMI差异：p<0.05）且体重指数无下降（BMI差异：p<0.001）。
化疗后，患者出现肌肉减少症，肌肉减少而脂肪组织增加，体重指数和体重减轻并不能充分反映这一情况，而影像学检查可以反映。特别是肌肉减少症患者接受的化疗周期较少，生存期较差。由于体重指数、体重和肌肉的减少与生存不良相关，早期（通过影像学）检测和预防（通过体育锻炼和营养）肌肉减少症可能会改善预后并降低化疗诱导的毒性。
