Head and Neck Unit, The Royal Marsden Hospital, London, UK.
Division of Clinical Studies, Institute of Cancer Research, London, UK.
Health Technol Assess. 2018 Apr;22(16):1-144. doi: 10.3310/hta22160.
Approximately 9000 new cases of head and neck squamous cell cancers (HNSCCs) are treated by the NHS each year. Chemoradiation therapy (CRT) is a commonly used treatment for advanced HNSCC. Approximately 90% of patients undergoing CRT require nutritional support via gastrostomy or nasogastric tube feeding. Long-term dysphagia following CRT is a primary concern for patients. The effect of enteral feeding routes on swallowing function is not well understood, and the two feeding methods have, to date (at the time of writing), not been compared. The aim of this pilot randomised controlled trial (RCT) was to compare these two options.
This was a mixed-methods multicentre study to establish the feasibility of a RCT comparing oral feeding plus pre-treatment gastrostomy with oral feeding plus as-required nasogastric tube feeding in patients with HNSCC. Patients were recruited from four tertiary centres treating cancer and randomised to the two arms of the study (using a 1 : 1 ratio). The eligibility criteria were patients with advanced-staged HNSCC who were suitable for primary CRT with curative intent and who presented with no swallowing problems.
The primary outcome was the willingness to be randomised. A qualitative process evaluation was conducted alongside an economic modelling exercise. The criteria for progression to a Phase III trial were based on a hypothesised recruitment rate of at least 50%, collection of outcome measures in at least 80% of those recruited and an economic value-of-information analysis for cost-effectiveness.
Of the 75 patients approached about the trial, only 17 consented to be randomised [0.23, 95% confidence interval (CI) 0.13 to 0.32]. Among those who were randomised, the compliance rate was high (0.94, 95% CI 0.83 to 1.05). Retention rates were high at completion of treatment (0.94, 95% CI 0.83 to 1.05), at the 3-month follow-up (0.88, 95% CI 0.73 to 1.04) and at the 6-month follow-up (0.88, 95% CI 0.73 to 1.04). No serious adverse events were recorded in relation to the trial. The qualitative substudy identified several factors that had an impact on recruitment, many of which are amenable to change. These included organisational factors, changing cancer treatments and patient and clinician preferences. A key reason for the differential recruitment between sites was the degree to which the multidisciplinary team gave a consistent demonstration of equipoise at all patient interactions at which supplementary feeding was discussed. An exploratory economic model generated from published evidence and expert opinion suggests that, over the 6-month model time horizon, pre-treatment gastrostomy tube feeding is not a cost-effective option, although this should be interpreted with caution and we recommend that this should not form the basis for policy. The economic value-of-information analysis indicates that additional research to eliminate uncertainty around model parameters is highly likely to be cost-effective.
The recruitment issues identified for this cohort may not be applicable to other populations undergoing CRT. There remains substantial uncertainty in the economic evaluation.
The trial did not meet one of the three criteria for progression, as the recruitment rate was lower than hypothesised. Once patients were recruited to the trial, compliance and retention in the trial were both high. The implementation of organisational and operational measures can increase the numbers recruited. The economic analysis suggests that further research in this area is likely to be cost-effective.
The implementation of organisational and operational measures can increase recruitment. The appropriate research question and design of a future study needs to be identified. More work is needed to understand the experiences of nasogastric tube feeding in patients undergoing CRT.
Current Controlled Trials ISRCTN48569216.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 22, No. 16. See the NIHR Journals Library website for further project information.
英国国家医疗服务体系（NHS）每年大约治疗 9000 例头颈部鳞状细胞癌（HNSCC）新病例。化学放射疗法（CRT）是治疗晚期 HNSCC 的常用方法。大约 90%接受 CRT 的患者需要通过胃造口术或鼻胃管喂养进行营养支持。CRT 后长期吞咽困难是患者的主要关注点。肠内喂养途径对吞咽功能的影响尚不清楚，这两种喂养方法迄今为止（在撰写本文时）尚未进行比较。本研究旨在比较这两种选择。
这是一项混合方法多中心研究，旨在确定一项 RCT 的可行性，该 RCT 比较了口腔喂养加术前胃造口术与口腔喂养加按需鼻胃管喂养在 HNSCC 患者中的应用。患者从四家治疗癌症的三级中心招募，并按照研究的两个臂（使用 1:1 比例）进行随机分组。纳入标准为适合根治性 CRT 的晚期 HNSCC 患者，且无吞咽问题。
主要结局是随机分组的意愿。同时进行了定性过程评估和经济建模研究。进入 III 期试验的标准基于假设的招募率至少为 50%，至少 80%招募的患者收集结局测量值，以及成本效益的价值信息分析。
在研究过程中，只有 17 名患者同意随机分组（0.23，95%置信区间（CI）0.13 至 0.32）。在随机分组的患者中，依从率很高（0.94，95%CI 0.83 至 1.05）。治疗结束时（0.94，95%CI 0.83 至 1.05）、3 个月随访时（0.88，95%CI 0.73 至 1.04）和 6 个月随访时（0.88，95%CI 0.73 至 1.04）的保留率也很高。与试验相关的严重不良事件未记录。定性子研究确定了影响招募的几个因素，其中许多因素是可以改变的。这些因素包括组织因素、癌症治疗的变化以及患者和临床医生的偏好。造成不同地点之间招募差异的一个关键原因是多学科团队在讨论补充喂养时，在所有患者互动中表现出平衡的一致程度。基于已发表证据和专家意见的探索性经济模型表明，在 6 个月的模型时间范围内，术前胃造口管喂养不是一种具有成本效益的选择，尽管这应该谨慎解释，我们建议这不应成为政策的基础。经济价值信息分析表明，消除模型参数不确定性的额外研究极有可能具有成本效益。
为该队列确定的招募问题可能不适用于其他接受 CRT 的人群。经济评估仍存在很大的不确定性。
由于招募率低于假设值，该试验未满足三个进展标准之一。一旦患者被招募到试验中，他们对试验的依从性和保留率都很高。实施组织和运营措施可以增加招募人数。经济分析表明，该领域的进一步研究很可能具有成本效益。
实施组织和运营措施可以增加招募人数。需要确定未来研究的适当研究问题和设计。需要进一步了解 CRT 患者鼻胃管喂养的经验。
当前对照试验 ISRCTN48569216。
本项目由英国国家卫生研究院（NIHR）健康技术评估计划资助，将在；第 22 卷，第 16 期。有关该项目的更多信息，请访问 NIHR 期刊库网站。
