BACKGROUND Low skeletal muscle index (SMI) in metastatic colorectal cancer (mCRC) patients is associated with poor outcomes. The prognostic impact of SMI changes during consecutive palliative systemic treatments is unknown. METHODS This is a retrospective analysis of the phase 3 CAIRO3 study. The CAIRO3 study randomized 557 patients between maintenance capecitabine + bevacizumab (CAP-B) or observation, after six cycles capecitabine + oxaliplatin + bevacizumab (CAPOX-B). Upon first disease progression (PD1), CAPOX-B was reintroduced until second progression (PD2). SMI was assessed by computed tomography (CT) (total 1355 scans). SMI and body mass index (BMI) changes were analyzed for three time-periods; p1: during initial CAPOX-B, p2: randomization to PD1, and p3: PD1 to PD2. The association between absolute and change in SMI and BMI (both per 1 standard deviation) during p1-p3, with PD1, PD2, and survival was studied by Cox regression models. RESULTS This analysis included 450 of the 557 patients randomized in the CAIRO3 study. Mean SMI decreased during p1: mean -0.6 SMI units [95% CI -1.07;-0.26] and p3: -2.2 units [-2.7;-1.8], whereas during p2, SMI increased + 1.2 units [0.8-1.6]. BMI changes did not reflect changes in SMI. SMI loss during p2 and p3 was significantly associated with shorter survival (HR 1.19 [1.09-1.35]; 1.54 [1.31-1.79], respectively). Sarcopenia at PD1 was significantly associated with early PD2 (HR 1.40 [1.10-1.70]). BMI loss independent of SMI loss was only associated with shorter overall survival during p3 (HR 1.35 [1.14-1.63]). CONCLUSIONS In mCRC patients, SMI loss during palliative systemic treatment was related with early disease progression and reduced survival. BMI did not reflect changes in SMI and could not identify patients at risk of poor outcome during early treatment lines.

中文翻译：

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转移性结直肠癌患者的骨骼肌指数损失和生存：3期CAIRO3试验的二级分析。

背景技术在转移性结直肠癌（mCRC）患者中低骨骼肌指数（SMI）与不良预后相关。连续的姑息性全身治疗期间SMI变化的预后影响尚不清楚。方法这是对CAIRO3 3期研究的回顾性分析。在六个周期的卡培他滨+奥沙利铂+贝伐单抗（CAPOX-B）后，CAIRO3研究将557名患者在维持卡培他滨+贝伐单抗（CAP-B）或观察之间随机分组。在第一个疾病进展（PD1）时，重新引入CAPOX-B，直到第二个疾病进展（PD2）。通过计算机断层扫描（CT）评估SMI（总共1355次扫描）。在三个时间段内分析了SMI和体重指数（BMI）的变化。p1：在初始CAPOX-B期间，p2：随机分配给PD1，p3：PD1到PD2。通过Cox回归模型研究了p1-p3期间PD1，PD2和生存率与SMI和BMI的绝对值和BMI的变化之间的关联（每1个标准差）。结果该分析包括在CAIRO3研究中随机分配的557例患者中的450例。在p1期间，平均SMI降低：平均-0.6 SMI单位[95％CI -1.07; -0.26]和p3：-2.2单位[-2.7; -1.8]，而在p2期间，SMI增加+ 1.2单位[0.8-1.6]。BMI更改未反映SMI中的更改。p2和p3期间SMI的丧失与生存期缩短显着相关（分别为HR 1.19 [1.09-1.35]； 1.54 [1.31-1.79]）。PD1的肌肉减少症与早期PD2显着相关（HR 1.40 [1.10-1.70]）。与SMI丢失无关的BMI丢失仅与p3期间的总体生存期较短有关（HR 1.35 [1.14-1.63]）。结论在mCRC患者中，姑息性全身治疗期间SMI的丧失与疾病的早期进展和生存期降低有关。BMI不能反映SMI的变化，也无法确定早期治疗线中有不良结局风险的患者。