There is no consensus on the optimal endpoint(s) in cancer cachexia trials. Endpoint variation is an obstacle when comparing interventions and their clinical value. The aim of this systematic review was to summarize and evaluate endpoints used to assess appetite and dietary intake in cancer cachexia clinical trials. A search for studies published from 1 January 1990 until 2 June 2021 was conducted using MEDLINE, Embase and Cochrane Central Register of Controlled Trials. Eligible studies examined cancer cachexia treatment versus a comparator in adults with assessments of appetite and/or dietary intake as study endpoints, a sample size ≥40 and an intervention lasting ≥14 days. Reporting was in line with PRISMA guidance, and a protocol was published in PROSPERO (2022 CRD42022276710). This review is part of a series of systematic reviews examining cachexia endpoints. Of the 5975 articles identified, 116 were eligible for the wider review series and 80 specifically examined endpoints of appetite (65 studies) and/or dietary intake (21 studies). Six trials assessed both appetite and dietary intake. Appetite was the primary outcome in 15 trials and dietary intake in 7 trials. Median sample size was 101 patients (range 40–628). Forty-nine studies included multiple primary tumour sites, while 31 studies involved single primary tumour sites (15 gastrointestinal, 7 lung, 7 head and neck and 2 female reproductive organs). The most frequently reported appetite endpoints were visual analogue scale (VAS) and numerical rating scale (NRS) (40%). The appetite item from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30/C15 PAL (38%) and the appetite question from North Central Cancer Treatment Group anorexia questionnaire (17%) were also frequently applied. Of the studies that assessed dietary intake, 13 (62%) used food records (prospective registrations) and 10 (48%) used retrospective methods (24-h recall or dietary history). For VAS/NRS, a mean change of 1.3 corresponded to Hedge's g of 0.5 and can be considered a moderate change. For food records, a mean change of 231 kcal/day or 11 g of protein/day corresponded to a moderate change. Choice of endpoint in cachexia trials will depend on factors pertinent to the trial to be conducted. Nevertheless, from trials assessed and available literature, NRS or EORTC QLQ C30/C15 PAL seems suitable for appetite assessments. Appetite and dietary intake endpoints are rarely used as primary outcomes in cancer cachexia. Dietary intake assessments were used mainly to monitor compliance and are not validated in cachexia populations. Given the importance to cachexia studies, dietary intake endpoints must be validated before they are used as endpoints in clinical trials.

中文翻译：

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癌症恶病质临床试验中的食欲和饮食摄入终点：恶病质终点系列的系统回顾 2

对于癌症恶病质试验的最佳终点尚未达成共识。在比较干预措施及其临床价值时，终点变异是一个障碍。本系统评价的目的是总结和评估癌症恶病质临床试验中用于评估食欲和饮食摄入的终点。使用 MEDLINE、Embase 和 Cochrane Central Register of Controlled Trials 检索 1990 年 1 月 1 日至 2021 年 6 月 2 日期间发表的研究。符合条件的研究以成人食欲和/或饮食摄入评估作为研究终点，对癌症恶病质治疗与对照进行比较，样本量≥40，干预持续≥14天。报告符合 PRISMA 指南，并在 PROSPERO 中发布了协议 (2022 CRD42022276710)。本综述是检查恶病质终点的一系列系统综述的一部分。在确定的 5975 篇文章中，116 篇符合更广泛的综述系列的条件，80 篇专门检​​查了食欲（65 项研究）和/或饮食摄入（21 项研究）的终点。六项试验评估了食欲和饮食摄入量。食欲是 15 项试验的主要结果，饮食摄入是 7 项试验的主要结果。中位样本量为 101 名患者（范围 40-628）。 49 项研究涉及多个原发肿瘤部位，31 项研究涉及单一原发肿瘤部位（15 项胃肠道、7 项肺、7 项头颈部和 2 项女性生殖器官）。最常报告的食欲终点是视觉模拟量表（VAS）和数字评定量表（NRS）（40%）。欧洲癌症研究与治疗组织生活质量问卷（EORTC QLQ）C30/C15 PAL（38%）中的食欲项目和中北部癌症治疗组厌食症问卷（17%）中的食欲问题也经常被应用。在评估膳食摄入量的研究中，13 项 (62%) 使用食物记录（前瞻性注册），10 项 (48%) 使用回顾性方法（24 小时回忆或饮食史）。对于 VAS/NRS，1.3 的平均变化对应于 0.5 的 Hedge g，可以被视为中等变化。对于食物记录，每天 231 kcal 或 11 g 蛋白质的平均变化相当于中等变化。恶病质试验中终点的选择将取决于与要进行的试验相关的因素。尽管如此，从评估的试验和现有文献来看，NRS 或 EORTC QLQ C30/C15 PAL 似乎适合食欲评估。食欲和饮食摄入终点很少用作癌症恶病质的主要结局。膳食摄入量评估主要用于监测依从性，并未在恶病质人群中得到验证。鉴于恶病质研究的重要性，膳食摄入终点在用作临床试验终点之前必须经过验证。