Golban Carina, Susa Septimiu-Radu, Varga Norberth-Istvan, Ivan Cristiana-Smaranda, Schirta Patricia Ortansa, Schirta Nicolae Călin, Negru Alina Gabriela, Saftescu Sorin, Negru Serban Mircea
Doctoral School, Department of General Medicine, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania.
Department of General Medicine, "Victor Babeş" University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania.
Cancers (Basel). 2025 Aug 25;17(17):2765. doi: 10.3390/cancers17172765.
Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis have become a standard in the treatment of all stages of non-small lung cancer. Beyond tumor-intrinsic biomarkers like PD-L1 expression, evidence points to the role of patient-related factors, such as body mass index, sarcopenia, and cachexia. These body composition parameters may reflect metabolic reserve or even immune competence and could help stratify outcomes in patients treated with PD-1 and PD-L1. This systematic review aims to evaluate the impact of body composition-specifically BMI, pretreatment weight loss, sarcopenia, and cachexia-on clinical outcomes such as progression-free and overall survival in NSCLC patients treated with immune checkpoint inhibitors. A systematic literature search was conducted across multiple databases including PubMed, Google Scholar, and Science Direct. We included full-text original research articles (1 January 2020-1 May 2025) reporting clinical outcomes of NSCLC patients treated with PD-1 or PD-L1 inhibitors, in relation to body composition factors (BMI, pretreatment weight loss, sarcopenia, cachexia). Eligible studies involved adults (>18 years) and included observational cohorts or controlled trials; animal or in vitro studies were excluded. Data extraction and risk of bias assessments were performed independently by two reviewers, with discrepancies being resolved through a third one. From 12,358 records identified, 21 studies met the inclusion criteria. Most were retrospective cohorts assessing the impact of pre-treatment weight loss, cachexia, and sarcopenia on ICI outcomes in NSCLC. These factors consistently predicted poorer survival and response, while BMI alone showed limited prognostic value. Considerable heterogeneity in body composition definitions and outcome reporting was observed. Body composition-particularly weight loss, cachexia, and sarcopenia-significantly impacts survival and response in NSCLC patients treated with ICIs. These factors reflect immune-metabolic dysfunction that may impair treatment efficacy. BMI alone is insufficient; routine assessment of muscle mass and cachexia could improve risk stratification.
靶向PD-1/PD-L1轴的免疫检查点抑制剂已成为非小细胞肺癌各阶段治疗的标准方法。除了诸如PD-L1表达等肿瘤内在生物标志物外，有证据表明患者相关因素也发挥作用，如体重指数、肌肉减少症和恶病质。这些身体成分参数可能反映代谢储备甚至免疫能力，并有助于对接受PD-1和PD-L1治疗的患者的预后进行分层。本系统评价旨在评估身体成分，特别是体重指数、治疗前体重减轻、肌肉减少症和恶病质，对接受免疫检查点抑制剂治疗的非小细胞肺癌患者的无进展生存期和总生存期等临床结局的影响。我们在包括PubMed、谷歌学术和科学Direct在内的多个数据库中进行了系统的文献检索。我们纳入了全文原始研究文章（2020年1月1日至2025年5月1日），这些文章报告了接受PD-1或PD-L1抑制剂治疗的非小细胞肺癌患者与身体成分因素（体重指数、治疗前体重减轻、肌肉减少症、恶病质）相关的临床结局。符合条件的研究涉及成年人（>18岁），包括观察性队列或对照试验；动物或体外研究被排除。数据提取和偏倚风险评估由两名审阅者独立进行，如有分歧则通过第三名审阅者解决。在识别出的12358条记录中，有21项研究符合纳入标准。大多数是回顾性队列研究，评估治疗前体重减轻、恶病质和肌肉减少症对非小细胞肺癌免疫检查点抑制剂治疗结局的影响。这些因素一致预测生存期和反应较差，而仅体重指数显示出有限的预后价值。在身体成分定义和结局报告方面观察到相当大的异质性。身体成分，特别是体重减轻、恶病质和肌肉减少症显著影响接受免疫检查点抑制剂治疗的非小细胞肺癌患者的生存期和反应。这些因素反映了可能损害治疗效果的免疫代谢功能障碍。仅体重指数是不够的；对肌肉质量和恶病质进行常规评估可以改善风险分层。
