Enlund Mats, Berglund Anders, Enlund Anna, Lundberg Johan, Wärnberg Fredrik, Wang Dong-Xin, Ekman Andreas, Ahlstrand Rebecca, Flisberg Per, Hedlund Lars, Östlund Ingrid, Bergkvist Leif
Centre for Clinical Research, Västmanland Hospital Västerås, University of Uppsala, Sweden.
Epistat AB, Uppsala, Sweden.
EClinicalMedicine. 2023 Jun 9;60:102037. doi: 10.1016/j.eclinm.2023.102037. eCollection 2023 Jun.
Anaesthesia may impact long-term cancer survival. In the Cancer and Anaesthesia study, we hypothesised that the hypnotic drug propofol will have an advantage of at least five percentage points in five-year survival over the inhalational anaesthetic sevoflurane for breast cancer surgery.
From 2118 eligible breast cancer patients scheduled for primary curable, invasive breast cancer surgery, 1764 were recruited after ethical approval and individual informed consent to this open label, single-blind, randomised trial at four county- and three university hospitals in Sweden and one Chinese university hospital. Of surveyed patients, 354 were excluded, mainly due to refusal to participate. Patients were randomised by computer at the monitoring organisation to general anaesthesia maintenance with either intravenous propofol or inhaled sevoflurane in a 1:1 ratio in permuted blocks. Data related to anaesthesia, surgery, oncology, and demographics were registered. The primary endpoint was five-year overall survival. Data are presented as Kaplan-Meier survival curves and Hazard Ratios based on Cox univariable regression analyses by both intention-to-treat and per-protocol. EudraCT, 2013-002380-25 and ClinicalTrials.gov, NCT01975064.
Of 1764 patients, included from December 3, 2013, to September 29, 2017, 1670 remained for analysis. The numbers who survived at least five years were 773/841 (91.9% (95% CI 90.1-93.8)) in the propofol group and 764/829 (92.2% (90.3-94.0)) in the sevoflurane group, (HR 1.03 (0.73-1.44); P = 0.875); the corresponding results in the per-protocol-analysis were: 733/798 (91.9% (90.0-93.8)) and 653/710 (92.0% (90.0-94.0)) (HR = 1.01 (0.71-1.44); P = 0.955). Survival after a median follow-up of 76.7 months did not indicate any difference between the groups (HR 0.97, 0.72-1.29; P = 0.829, log rank test).
No difference in overall survival was found between general anaesthesia with propofol or sevoflurane for breast cancer surgery.
Swedish Research Council; Uppsala-Örebro Regional Research Council; Västmanland Regional Research Fund; Västmanland Cancer Foundation; Stig and Ragna Gohrton Foundation; Birgit and Henry Knutsson Foundation.
麻醉可能会影响癌症患者的长期生存。在癌症与麻醉研究中，我们假设对于乳腺癌手术，催眠药物丙泊酚在五年生存率方面比吸入麻醉药七氟醚至少有五个百分点的优势。
在瑞典的四家县级医院和三家大学医院以及一家中国大学医院，对2118例计划进行原发性可治愈性浸润性乳腺癌手术的符合条件的乳腺癌患者进行研究，经伦理批准和个人知情同意后，1764例患者被纳入这项开放标签、单盲、随机试验。在接受调查的患者中，354例被排除，主要原因是拒绝参与。患者在监测机构通过计算机以1:1的比例在置换区组中随机分配接受静脉注射丙泊酚或吸入七氟醚进行全身麻醉维持。记录与麻醉、手术、肿瘤学和人口统计学相关的数据。主要终点是五年总生存率。数据以Kaplan-Meier生存曲线和基于Cox单变量回归分析的风险比呈现，分析采用意向性分析和符合方案分析。欧洲临床试验数据库编号：2013-002380-25，美国国立医学图书馆临床试验注册中心编号：NCT01975064。
在2013年12月3日至2017年9月29日纳入的1764例患者中，1670例患者纳入分析。丙泊酚组至少存活五年的患者有773/841例（91.9%（95%CI 90.1-93.8）），七氟醚组有764/829例（92.2%（90.3-94.0）），（风险比1.03（0.73-1.44）；P = 0.875）；符合方案分析的相应结果为：733/798例（91.9%（90.0-93.8））和653/710例（92.0%（90.0-94.0））（风险比 = 1.01（0.71-1.44）；P = 0.955）。中位随访76.7个月后的生存率未显示两组之间存在任何差异（风险比0.97，0.72-1.29；P = 0.829，对数秩检验）。
对于乳腺癌手术，丙泊酚或七氟醚全身麻醉在总生存率方面没有差异。
瑞典研究理事会；乌普萨拉-厄勒布鲁地区研究理事会；韦斯曼兰地区研究基金；韦斯曼兰癌症基金会；斯蒂格和拉格纳·戈尔通基金会；比吉特和亨利·克努特松基金会。
