The value of FDG positron emission tomography/computerised tomography (PET/CT) in pre-operative staging of colorectal cancer: a systematic review and economic evaluation.
The value of FDG positron emission tomography/computerised tomography (PET/CT) in pre-operative staging of colorectal cancer: a systematic review and economic evaluation.
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FDG 正电子发射断层扫描/计算机断层扫描 (PET/CT) 在结直肠癌术前分期中的价值：系统评价和经济评估。
DOI：
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发表时间：
2011
影响因子：
3.6
通讯作者：
M. Dunlop
中科院分区：
文献类型：
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作者：
J. Brush;K. Boyd;F. Chappell;F. Crawford;M. Dozier;E. Fenwick;Julie May Glanville;H. Mcintosh;A. Renehan;D. Weller;M. Dunlop
目标
在英国，结直肠癌（CRC）是第三常见的恶性肿瘤（仅次于肺癌和乳腺癌），2006年登记了37，514例病例：约三分之二（23，384）在结肠，三分之一（14，130）在直肠。结肠癌的治疗可以有很大的不同，但手术切除是治疗的主要目的。手术切除后，对肿瘤、其侵袭特征和扩散（肿瘤分期）进行全面评估。在CRC的术前分期中使用了许多成像模式，包括计算机断层扫描（CT）、磁共振成像、超声成像和正电子发射断层扫描（PET）。本报告探讨了CT与PET扫描（PET/CT“混合”扫描）相结合的作用。研究目标是：使用系统回顾方法评价氟-18-脱氧葡萄糖（FDG）PET/CT对原发性、复发性和转移性癌症术前分期的诊断准确性和治疗影响;进行概率决策分析建模（使用Monte Carlo模拟）;并进行信息分析价值，以帮助告知是否有潜在的价值进行进一步研究。
数据源
对于研究的每一个方面-系统综述、手工检索研究和经济评价-通过全面检索已发表和未发表的研究，包括数据库检索、参考文献清单检索和与专家联系，建立了一个数据库。在系统性综述中，前瞻性和回顾性患者系列（诊断队列）和随机对照试验（RCT）符合入选条件。包括连续系列和未明确报告为连续的系列。
复习方法
两名评审员提取所有数据，独立应用标准，并通过讨论解决分歧。提取了用于填充2 × 2列联表的数据，包括使用研究自身定义的真阳性、真阴性、假阳性和假阴性数量，以及与管理变更相关的数据。使用诊断准确性研究质量评估检查表中的14个项目评估纳入研究的方法学质量。使用患者水平数据计算灵敏度和特异性以及置信区间（CI）。数据以森林图的形式绘制。为了进行经济评估，针对每种疾病状态设计了经济模型：原发性、复发性和转移性。根据各种信息来源（特别是已发表的数据来源）和文献，并与临床专家协商，开发和填充这些数据。
结果
审查发现30项研究符合合格标准。只有两项小型研究评价了FDG PET/CT在原发性CRC中的应用，目前还没有足够的证据支持其常规应用。使用FDG PET/CT检测复发性疾病的数据来自5项回顾性研究，其中观察到的合并敏感性为91%（95% CI 0.87%至0.95%），特异性为91%（95% CI 0.85%至0.95%）。来自疑似转移性疾病分期患者的汇总准确性数据显示，FDG PET/CT的汇总敏感性为91%（95% CI 87%至94%），特异性为76%（95% CI 58%至88%），但研究质量较差意味着数据的有效性可能会受到几种偏倚的影响。单独的手动搜索研究未产生任何与FDG PET/CT相关的额外独特研究。复发性疾病模型显示，直肠癌的增量成本效益比为每质量调整生命年（QALY）21，409英镑，结肠癌为每QALY 6189英镑，转移性疾病为每QALY 21，434英镑。手工检索的价值，以确定研究不明确定义或报告的诊断测试仍有待调查。
结论
该系统综述发现，没有足够的证据支持在原发性CRC中常规使用FDG PET/CT，只有少量证据支持其在复发性和转移性CRC的术前分期中的使用，尽管FDG PET/CT被证明可以改变患者的管理，但数据存在分歧，研究质量普遍较差。手动搜索以识别定义或报告不太明确的诊断测试的研究，没有发现其他研究。经济评价的主要局限性是由于不确定性和缺乏五个模型中每个模型关键参数的系统性审查的可用证据。为了解决这一问题，在选择模型参数的DTA估计值时采用了保守方法。对每个模型进行了概率分析，特别是对DTA估计，纳入了广泛的不确定性。没有一个经济模型报告节省了费用，但由于缺乏最新信息，为了确定更可靠的结果，所采用的方法是保守的。经济评价得出结论，FDG PET/CT作为附加成像设备在复发性结肠癌、复发性直肠癌和转移性疾病的术前分期中具有成本效益，但在原发性结肠癌或直肠癌中不具有成本效益。进行一项随机对照试验，同时进行经济评价，以评价FDG PET/CT与传统成像（无PET）相比对复发性和转移性CRC术前分期的治疗影响和成本效益，这将是有价值的。
OBJECTIVES
In the UK, colorectal cancer (CRC) is the third most common malignancy (behind lung and breast cancer) with 37,514 cases registered in 2006: around two-thirds (23,384) in the colon and one-third (14,130) in the rectum. Treatment of cancers of the colon can vary considerably, but surgical resection is the mainstay of treatment for curative intent. Following surgical resection, there is a comprehensive assessment of the tumour, it's invasion characteristics and spread (tumour staging). A number of imaging modalities are used in the pre-operative staging of CRCs including; computerised tomography (CT), magnetic resonance imaging, ultrasound imaging and positron emission tomography (PET). This report examines the role of CT in combination with PET scanning (PET/CT 'hybrid' scan). The research objectives are: to evaluate the diagnostic accuracy and therapeutic impact of fluorine-18-deoxyglucose (FDG) PET/CT for the pre-operative staging of primary, recurrent and metastatic cancer using systematic review methods; undertake probabilistic decision-analytic modelling (using Monte Carlo simulation); and conduct a value of information analysis to help inform whether or not there is potential worth in undertaking further research.
DATA SOURCES
For each aspect of the research - the systematic review, the handsearch study and the economic evaluation - a database was assembled from a comprehensive search for published and unpublished studies, which included database searches, reference lists search and contact with experts. In the systematic review prospective and retrospective patient series (diagnostic cohort) and randomised controlled trials (RCTs) were eligible for inclusion. Both consecutive series and series that are not explicitly reported as consecutive were included.
REVIEW METHODS
Two reviewers extracted all data and applied the criteria independently and resolved disagreements by discussion. Data to populate 2 × 2 contingency tables consisting of the number of true positives, true negatives, false positives and false negatives using the studies' own definitions were extracted, as were data relating to changes in management. Fourteen items from the Quality Assessment of Diagnostic Accuracy Studies checklist were used to assess the methodological quality of the included studies. Patient-level data were used to calculate sensitivity and specificity with confidence intervals (CIs). Data were plotted graphically in forest plots. For the economic evaluation, economic models were designed for each of the disease states: primary, recurrent and metastatic. These were developed and populated based on a variety of information sources (in particular from published data sources) and literature, and in consultation with clinical experts.
RESULTS
The review found 30 studies that met the eligibility criteria. Only two small studies evaluated the use of FDG PET/CT in primary CRC, and there is insufficient evidence to support its routine use at this time. The use of FDG PET/CT for the detection of recurrent disease identified data from five retrospective studies from which a pooled sensitivity of 91% (95% CI 0.87% to 0.95%) and specificity of 91% (95% CI 0.85% to 0.95%) were observed. Pooled accuracy data from patients undergoing staging for suspected metastatic disease showed FDG PET/CT to have a pooled sensitivity of 91% (95% CI 87% to 94%) and a specificity of 76% (95% CI 58% to 88%), but the poor quality of the studies means the validity of the data may be compromised by several biases. The separate handsearch study did not yield any additional unique studies relevant to FDG PET/CT. Models for recurrent disease demonstrated an incremental cost-effectiveness ratio of £ 21,409 per quality-adjusted life-year (QALY) for rectal cancer, £ 6189 per QALY for colon cancer and £ 21,434 per QALY for metastatic disease. The value of handsearching to identify studies of less clearly defined or reported diagnostic tests is still to be investigated.
CONCLUSIONS
The systematic review found insufficient evidence to support the routine use of FDG PET/CT in primary CRC and only a small amount of evidence supporting its use in the pre-operative staging of recurrent and metastatic CRC, and, although FDG PET/CT was shown to change patient management, the data are divergent and the quality of research is generally poor. The handsearch to identify studies of less clearly defined or reported diagnostic tests did not find additional studies. The primary limitations in the economic evaluations were due to uncertainty and lack of available evidence from the systematic reviews for key parameters in each of the five models. In order to address this, a conservative approach was adopted in choosing DTA estimates for the model parameters. Probabilistic analyses were undertaken for each of the models, incorporating wide levels of uncertainty particularly for the DTA estimates. None of the economic models reported cost-savings, but the approach adopted was conservative in order to determine more reliable results given the lack of current information. The economic evaluations conclude that FDG PET/CT as an add-on imaging device is cost-effective in the pre-operative staging of recurrent colon, recurrent rectal and metastatic disease but not in primary colon or rectal cancers. There would be value in undertaking an RCT with a concurrent economic evaluation to evaluate the therapeutic impact and cost-effectiveness of FDG PET/CT compared with conventional imaging (without PET) for the pre-operative staging of recurrent and metastatic CRC.