Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.
University of Alberta Libraries, University of Alberta, Edmonton, AB, Canada.
J Cachexia Sarcopenia Muscle. 2023 Oct;14(5):1918-1931. doi: 10.1002/jcsm.13318. Epub 2023 Sep 7.
Investigators are increasingly measuring skeletal muscle (SM) and adipose tissue (AT) change during cancer treatment to understand impact on patient outcomes. Recent meta-analyses have reported high heterogeneity in this literature, representing uncertainty in the resulting estimates. Using the setting of palliative-intent chemotherapy as an exemplar, we aimed to systematically summarize the sources of variability among studies evaluating SM and AT change during cancer treatment and propose standards for future studies to enable reliable meta-analysis. Studies that measured computed tomography-defined SM and/or AT change in adult patients during palliative-intent chemotherapy for solid tumours were included, with no date or geographical limiters. Of 2496 publications screened by abstract/title, 83 were reviewed in full text and 38 included for extraction, representing 34 unique cohorts across 8 tumour sites. The timing of baseline measurement was frequently defined as prior to treatment, while endpoint timing ranged from 6 weeks after treatment start to time of progression. Fewer than 50% specified the actual time interval between measurements. Measurement error was infrequently discussed (8/34). A single metric (cm /m , cm or %) was used to describe SM change in 18/34 cohorts, while multiple metrics were presented for 10/34 and no descriptive metrics for 6/34. AT change metrics and sex-specific reporting were available for 10/34 cohorts. Associations between SM loss and overall survival were evaluated in 24 publications, with classification of SM loss ranging from any loss to >14% loss over variable time intervals. Age and sex were the most common covariates, with disease response in 50% of models. Despite a wealth of data and effort, heterogeneity in study design, reporting and statistical analysis hinders evidence synthesis regarding the severity and outcomes of SM and AT change during cancer treatment. Proposed standards for study design include selection of homogenous cohorts, clear definition of baseline/endpoint timing and attention to measurement error. Standard reporting should include baseline SM and AT by sex, actual scan interval, SM and AT change using multiple metrics and visualization of the range of change observed. Reporting by sex would advance understanding of sexual dimorphism in SM and AT change. Evaluating the impact of tissue change on outcomes requires adjustment for relevant covariates and concurrent disease response. Adoption of these standards by researchers and publishers would alter the current paradigm to enable meta-analysis of future studies and move the field towards meaningful application of SM and AT change to clinical care.
研究人员越来越多地测量癌症治疗过程中的骨骼肌 (SM) 和脂肪组织 (AT) 变化，以了解其对患者结局的影响。最近的荟萃分析报告称，这方面的文献存在高度异质性，这表明由此产生的估计值存在不确定性。我们以姑息性化疗为范例，旨在系统总结评估癌症治疗过程中 SM 和 AT 变化的研究中存在的变异性来源，并提出未来研究的标准，以实现可靠的荟萃分析。纳入了评估实体瘤姑息性化疗患者 SM 和/或 AT 变化的成年患者的计算机断层扫描定义的 SM 和/或 AT 变化的研究，无日期或地理限制。在 2496 篇经摘要/标题筛选的论文中，有 83 篇全文审查，38 篇进行了提取，代表 8 个肿瘤部位的 34 个独特队列。基线测量的时间通常定义为治疗前，而终点时间范围从治疗开始后 6 周到进展时。不到 50%的研究报告了实际测量间隔。只有 8/34 篇研究讨论了测量误差。18/34 个队列中使用了单一指标 (cm/m ，cm 或 %) 来描述 SM 变化，10/34 个队列中呈现了多个指标，6/34 个队列中没有描述性指标。有 10/34 个队列提供了 AT 变化指标和性别特异性报告。24 篇出版物评估了 SM 丢失与总生存期之间的关系，SM 丢失的分类范围从任意丢失到不同时间间隔的>14%丢失。年龄和性别是最常见的协变量，50%的模型中有疾病反应。尽管有大量的数据和努力，但研究设计、报告和统计分析的异质性阻碍了关于癌症治疗过程中 SM 和 AT 变化的严重程度和结局的证据综合。建议的研究设计标准包括选择同质队列、明确基线/终点时间的定义以及关注测量误差。标准报告应包括按性别报告基线 SM 和 AT 、实际扫描间隔、使用多个指标报告 SM 和 AT 变化以及显示观察到的变化范围。按性别报告将有助于了解 SM 和 AT 变化中的性别二态性。评估组织变化对结局的影响需要调整相关协变量和同时发生的疾病反应。研究人员和出版商采用这些标准将改变当前的范式，以实现对未来研究的荟萃分析，并使该领域朝着将 SM 和 AT 变化应用于临床护理的方向迈进。
