Barber Addison, Willbanks Amber, Abplanalp Kathryn, Lewis Christopher W, Binder-Markey Ben, Jayabalan Prakash, Lieber Richard L, Roy Ishan
Shirley Ryan AbilityLab (formerly known as Rehabilitation Institute of Chicago), Chicago, Illinois, USA.
Hines VA Medical Center, Maywood, Illinois, USA.
J Cachexia Sarcopenia Muscle. 2025 Aug;16(4):e70024. doi: 10.1002/jcsm.70024.
Decline in functional independence is a defining event of cancer cachexia, and attempts at creating cachexia-specific therapies have largely failed because of the inability to identify treatments that improve functional capacity. This may be, in part, due to a lack of outcomes that are appropriate and sensitive enough to detect functional recovery. Grip strength is a frequently used outcome measure in cachexia clinical studies; however, the use of gait-based measures is now emerging. These two outcome measures have never been directly compared in the same cohort of cachexia patients regarding their ability to measure and relationship to functional independence. We hypothesize that gait-based measures more comprehensively act as a proxy measure for functional independence related to cachexia.
In a retrospective cohort study of 485 cancer patients with a range of cachexia severity and related functional decline who required care at a single-centre inpatient rehabilitation facility (IRF), we assessed the six-minute walk test (6MWT) and hand grip strength (hGS) as proxy measures for functional capacity. Functional capacity is defined as mobility and activities of daily living (ADLs), is quantified by measures of functional independence and referred to here as the Total Motor Score. Cachexia patients were identified primarily using the Fearon et al. consensus criteria, with secondary identification by the Weight Loss Grading Scale (WLGS), Prognostic Nutritional Index (PNI) and neutrophil-to-lymphocyte ratio (NLR). Primary outcomes were change/gain in Total Motor Score, IRF discharge destination (e.g., homebound status or need for care facility) and 6-month survival.
The presence of cachexia in this cohort was 63%. This cohort was 52% male. Mean age was 63 ± 0.63 (SEM) years. Multivariate linear regression demonstrated that change in 6MWT (p < 0.0001) but not hGS (p = 0.084) correlated with Total Motor Score gain after controlling for age, disease burden, cancer type, previous cancer treatment and baseline motor function as covariates. Area under the curve analysis revealed that change in 6MWT (p < 0.0001, AUC = 0.77) was a stronger predictor of Total Motor Score gain than hGS (p = 0.0016, AUC = 0.59). In a multivariate logistic regression model, discharge from IRF to home with independence was predicted by change in 6MWT (p = 0.0007) but not hGS (p = 0.8075). Six-month survival post-rehabilitation was predicted by change in 6MWT (p = 0.0345) but not hGS (p = 0.9025) in a multivariate Cox proportional hazards model.
Multiple analytical approaches to our data set demonstrate that changes in 6MWT are better associated with cachexia-related outcomes and should be included in future cachexia studies.
功能独立性下降是癌症恶病质的一个标志性事件，由于无法确定能改善功能能力的治疗方法，开发针对恶病质的特异性疗法的尝试大多以失败告终。这可能部分归因于缺乏足够合适且敏感的指标来检测功能恢复情况。握力是恶病质临床研究中常用的一项指标；然而，基于步态的指标目前也逐渐受到关注。在同一组恶病质患者中，尚未对这两种指标在测量功能以及与功能独立性的关系方面进行直接比较。我们推测，基于步态的指标能更全面地作为与恶病质相关的功能独立性的替代指标。
在一项对485例癌症患者的回顾性队列研究中，这些患者恶病质严重程度各异且伴有相关功能下降，在一家单中心住院康复机构（IRF）接受治疗。我们评估了六分钟步行试验（6MWT）和握力（hGS）作为功能能力的替代指标。功能能力定义为活动能力和日常生活活动（ADL），通过功能独立性测量进行量化，在此称为总运动评分。主要通过费伦等人的共识标准来识别恶病质患者，辅助标准包括体重减轻分级量表（WLGS）、预后营养指数（PNI）和中性粒细胞与淋巴细胞比值（NLR）。主要结局指标包括总运动评分的变化/增加、IRF出院去向（例如，居家状态或对护理机构的需求）以及6个月生存率。
该队列中恶病质的发生率为63%。该队列中男性占52%。平均年龄为63±0.63（SEM）岁。多变量线性回归显示，在将年龄、疾病负担、癌症类型、既往癌症治疗和基线运动功能作为协变量进行控制后，6MWT的变化（p<0.0001）与总运动评分的增加相关，而hGS的变化（p = 0.084）与之无关。曲线下面积分析表明，6MWT的变化（p<0.0001，AUC = 0.77）比hGS的变化（p = 0.0016，AUC = 0.59）更能预测总运动评分的增加。在多变量逻辑回归模型中，6MWT的变化（p = 0.0007）可预测从IRF独立出院回家，而hGS的变化（p = 0.8075）则不能。在多变量Cox比例风险模型中，6MWT的变化（p = 0.0345）可预测康复后6个月的生存率，而hGS的变化（p = 0.9025）则不能。
对我们数据集的多种分析方法表明，6MWT的变化与恶病质相关结局的关联性更强，应纳入未来的恶病质研究中。
