Aktas Aynur, Kadakia Kunal C, Waldman Jake, Walsh Declan
Department of Supportive Oncology, Levine Cancer Institute, Atrium Health, Charlotte, North Carolina, USA.
Department of Medical Oncology, Levine Cancer Institute, Atrium Health, Charlotte, North Carolina, USA.
J Cachexia Sarcopenia Muscle. 2025 Apr;16(2):e13754. doi: 10.1002/jcsm.13754.
Accurate toxicity reporting in cancer clinical trials is necessary to promote regulatory decision making. Up to 85% of those with some cancers (e.g., oesophagus, head and neck, and pancreas) experience significant progressive weight loss (WL) throughout treatment. Therefore, it is necessary that investigators accurately grade and report WL. We have identified two dangerous and misleading approaches in the CTCAE specific to WL: (1) severity grades and associated clinical descriptions and (2) lack of pretreatment weight and longitudinal weight changes. This review highlights the critical importance of a more accurate, comprehensive and patient-focused WL assessment in oncology clinical trials and the CTCAE. We offer a path forward for identification and management of this life-threatening phenomenon, whether it is due to cancer or an antitumor treatment. The National Cancer Institute should consider the following five ideas and concrete action items for future CTCAE versions: (1) Weight assessment has important implications for toxicity determination and prognosis in clinical trials and should be consistently integrated into study reports; (2) Adverse event assessment should be patient-focused and supported by clinically relevant definitions of each grade level; (3) the CTCAE grades and associated clinical descriptions for WL should be revised to better reflect the impact of WL on trial endpoints and patient safety; (4) WL should be assessed as a continuous variable to capture duration, severity, and trajectory; and (5) WL should be urgently incorporated into the PRO-CTCAE to define the individual impact.
在癌症临床试验中进行准确的毒性报告对于促进监管决策至关重要。高达85%的某些癌症患者(如食管癌、头颈癌和胰腺癌)在整个治疗过程中会出现显著的进行性体重减轻(WL)。因此,研究人员准确分级并报告体重减轻情况很有必要。我们在CTCAE中发现了两种针对体重减轻的危险且具有误导性的方法:(1)严重程度分级及相关临床描述;(2)缺乏治疗前体重和纵向体重变化。本综述强调了在肿瘤临床试验和CTCAE中进行更准确、全面且以患者为中心的体重减轻评估的至关重要性。我们为识别和管理这种危及生命的现象提供了一条前进的道路,无论其是由癌症还是抗肿瘤治疗引起的。美国国立癌症研究所应在未来CTCAE版本中考虑以下五个想法和具体行动项目:(1)体重评估对临床试验中的毒性判定和预后具有重要意义,应始终纳入研究报告;(2)不良事件评估应以患者为中心,并由每个等级水平的临床相关定义提供支持;(3)应修订CTCAE中体重减轻的分级及相关临床描述,以更好地反映体重减轻对试验终点和患者安全的影响;(4)体重减轻应作为一个连续变量进行评估,以捕捉持续时间、严重程度和变化轨迹;(5)应将体重减轻紧急纳入PRO-CTCAE以定义个体影响。