Picot Jo, Copley Vicky, Colquitt Jill L, Kalita Neelam, Hartwell Debbie, Bryant Jackie
Southampton Health Technology Assessments Centre (SHTAC), University of Southampton, Southampton, UK.
Health Technol Assess. 2015 Aug;19(69):1-190. doi: 10.3310/hta19690.
Initial treatment for early breast cancer is usually either breast-conserving surgery (BCS) or mastectomy. After BCS, whole-breast external beam radiotherapy (WB-EBRT) is the standard of care. A potential alternative to post-operative WB-EBRT is intraoperative radiation therapy delivered by the INTRABEAM(®) Photon Radiotherapy System (Carl Zeiss, Oberkochen, Germany) to the tissue adjacent to the resection cavity at the time of surgery.
To assess the clinical effectiveness and cost-effectiveness of INTRABEAM for the adjuvant treatment of early breast cancer during surgical removal of the tumour.
Electronic bibliographic databases, including MEDLINE, EMBASE and The Cochrane Library, were searched from inception to March 2014 for English-language articles. Bibliographies of articles, systematic reviews, clinical guidelines and the manufacturer's submission were also searched. The advisory group was contacted to identify additional evidence.
Systematic reviews of clinical effectiveness, health-related quality of life and cost-effectiveness were conducted. Two reviewers independently screened titles and abstracts for eligibility. Inclusion criteria were applied to full texts of retrieved papers by one reviewer and checked by a second reviewer. Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer, and differences in opinion were resolved through discussion at each stage. Clinical effectiveness studies were included if they were carried out in patients with early operable breast cancer. The intervention was the INTRABEAM system, which was compared with WB-EBRT, and study designs were randomised controlled trials (RCTs). Controlled clinical trials could be considered if data from available RCTs were incomplete (e.g. absence of data on outcomes of interest). A cost-utility decision-analytic model was developed to estimate the costs, benefits and cost-effectiveness of INTRABEAM compared with WB-EBRT for early operable breast cancer.
One non-inferiority RCT, TARGeted Intraoperative radioTherapy Alone (TARGIT-A), met the inclusion criteria for the review. The review found that local recurrence was slightly higher following INTRABEAM than WB-EBRT, but the difference did not exceed the 2.5% non-inferiority margin providing INTRABEAM was given at the same time as BCS. Overall survival was similar with both treatments. Statistically significant differences in complications were found for the occurrence of wound seroma requiring more than three aspirations (more frequent in the INTRABEAM group) and for a Radiation Therapy Oncology Group toxicity score of grade 3 or 4 (less frequent in the INTRABEAM group). Cost-effectiveness base-case analysis indicates that INTRABEAM is less expensive but also less effective than WB-EBRT because it is associated with lower total costs but fewer total quality-adjusted life-years gained. However, sensitivity analyses identified four model parameters that can cause a switch in the treatment option that is considered cost-effective.
The base-case result from the model is subject to uncertainty because the disease progression parameters are largely drawn from the single available RCT. The RCT median follow-up of 2 years 5 months may be inadequate, particularly as the number of participants with local recurrence is low. The model is particularly sensitive to this parameter.
A significant investment in INTRABEAM equipment and staff training (clinical and non-clinical) would be required to make this technology available across the NHS. Longer-term follow-up data from the TARGIT-A trial and analysis of registry data are required as results are currently based on a small number of events and economic modelling results are uncertain.
This study is registered as PROSPERO CRD42013006720.
The National Institute for Health Research Health Technology Assessment programme. Note that the economic model associated with this document is protected by intellectual property rights, which are owned by the University of Southampton. Anyone wishing to modify, adapt, translate, reverse engineer, decompile, dismantle or create derivative work based on the economic model must first seek the agreement of the property owners.
早期乳腺癌的初始治疗通常是保乳手术（BCS）或乳房切除术。保乳手术后，全乳外照射放疗（WB-EBRT）是标准治疗方法。术中放疗是术后WB-EBRT的一种潜在替代方案，可通过INTRABEAM（®）光子放疗系统（德国奥伯科亨卡尔蔡司公司）在手术时对切除腔附近的组织进行放疗。
评估INTRABEAM在手术切除肿瘤期间辅助治疗早期乳腺癌的临床疗效和成本效益。
检索电子文献数据库，包括MEDLINE、EMBASE和Cochrane图书馆截至2014年3月的英文文章。还检索了文章的参考文献、系统评价、临床指南和制造商提交的资料。联系咨询小组以确定其他证据。
对临床疗效、健康相关生活质量和成本效益进行系统评价。两名评价者独立筛选标题和摘要以确定是否符合纳入标准。一名评价者将纳入标准应用于检索到的论文全文，并由另一名评价者进行核对。数据提取和质量评估由一名评价者进行，并由另一名评价者进行核对，意见分歧通过各阶段的讨论解决。如果临床疗效研究是在早期可手术乳腺癌患者中进行的，则纳入研究。干预措施为INTRABEAM系统，将其与WB-EBRT进行比较，研究设计为随机对照试验（RCT）。如果现有RCT的数据不完整（例如缺乏感兴趣结局的数据），则可考虑纳入对照临床试验。建立了成本效用决策分析模型，以估计INTRABEAM与WB-EBRT相比在早期可手术乳腺癌中的成本、效益和成本效益。
一项非劣效性RCT，即单独靶向术中放疗（TARGIT-A），符合该评价的纳入标准。评价发现，INTRABEAM治疗后局部复发率略高于WB-EBRT，但差异未超过2.5%的非劣效性界值，前提是INTRABEAM与BCS同时进行。两种治疗的总生存率相似。在需要超过三次抽吸的伤口血清肿发生率（INTRABEAM组更常见）和放射治疗肿瘤学组3级或4级毒性评分（INTRABEAM组较少见）方面，并发症存在统计学显著差异。成本效益基本案例分析表明，INTRABEAM成本较低，但效果也不如WB-EBRT，因为它的总成本较低，但获得的总质量调整生命年较少。然而，敏感性分析确定了四个模型参数，这些参数可能导致被认为具有成本效益的治疗方案发生转变。
该模型的基本案例结果存在不确定性，因为疾病进展参数主要来自唯一可用的RCT。RCT的中位随访时间为2年5个月，可能不够充分，特别是因为局部复发的参与者数量较少。该模型对该参数特别敏感。
要使该技术在英国国家医疗服务体系（NHS）中广泛应用，需要对INTRABEAM设备和人员培训（临床和非临床）进行大量投资。需要TARGIT-A试验的长期随访数据和登记数据的分析，因为目前的结果基于少量事件，经济建模结果不确定。
本研究注册为PROSPERO CRD42（2013）006720。
英国国家卫生研究院卫生技术评估计划。请注意，与本文相关的经济模型受知识产权保护，归南安普顿大学所有。任何希望修改、改编、翻译、反向工程、反编译、拆解或基于该经济模型创建衍生作品的人，必须首先寻求产权所有者的同意。
