Kagenaar Eva, Lugo-Palacios David G, Hutchings Andrew, Aggarwal Ajay, O'Neill Stephen, Rachet Bernard, Edwards John, Faivre-Finn Corinne, Grieve Richard
Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine Faculty of Public Health and Policy, London, UK.
London School of Hygiene and Tropical Medicine, London, UK.
BMJ Open. 2025 Jul 13;15(7):e103038. doi: 10.1136/bmjopen-2025-103038.
Randomised controlled trials have aimed to assess the effectiveness of stereotactic ablative radiotherapy (SABR) with curative intent versus surgical resection for individuals diagnosed with early-stage non-small cell lung cancer (NSCLC) but have failed to recruit sufficient numbers of patients. Non-randomised studies for early-stage NSCLC have reported mixed outcomes following curative SABR versus surgical resection, but did not fully address confounding by indication. The Surgery Or RadioTherapy for early-stage cancer study (SORT) will assess the comparative effectiveness of SABR with curative intent versus surgical resection for NSCLC with a target trial emulation approach, as this can reduce biases in observational studies that aim to estimate the causal effect of interventions.
The SORT study will use the National Cancer Registry for individuals diagnosed with early-stage NSCLC in England during 2015-2020 (inclusive) who received SABR with curative intent or surgical resection. These data will be linked to Hospital Episode Statistics, National Radiotherapy Data Set and the Systemic Anti-Cancer Therapy dataset to obtain information on clinical and sociodemographic characteristics and the treatment received. This target trial emulation will define study population eligibility criteria and regimens for SABR with curative intent and surgical resection. We will reduce the risk of residual confounding with instrumental variable analyses that will exploit geographical variation across the National Health Service in England in the use of SABR with curative intent versus surgical resection for early-stage NSCLC. The primary outcome will be 3-year all-cause mortality after treatment initiation. Secondary outcomes will include 3-month, 6-month, 12-month and 24-month all-cause and lung-cancer mortality, time to death, numbers of hospitalisations, incremental costs and incremental cost-effectiveness.
Ethical approval was obtained from the London School of Hygiene and Tropical Medicine Research Ethics Committee (reference number 29 717-1). Results will be disseminated to clinicians, patients, policy-makers and researchers.
随机对照试验旨在评估立体定向消融放疗（SABR）与手术切除对确诊为早期非小细胞肺癌（NSCLC）患者的疗效，但未能招募到足够数量的患者。早期NSCLC的非随机研究报告了根治性SABR与手术切除后的不同结果，但未充分解决指征性混杂问题。早期癌症的手术或放疗研究（SORT）将采用目标试验模拟方法评估根治性SABR与手术切除对NSCLC的相对疗效，因为这可以减少旨在估计干预因果效应的观察性研究中的偏差。
SORT研究将使用国家癌症登记处的数据，这些数据来自2015年至2020年（含）期间在英格兰被诊断为早期NSCLC并接受了根治性SABR或手术切除的患者。这些数据将与医院事件统计、国家放疗数据集和全身抗癌治疗数据集相链接，以获取临床和社会人口学特征以及所接受治疗的信息。这种目标试验模拟将定义研究人群的纳入标准以及根治性SABR和手术切除的治疗方案。我们将通过工具变量分析降低残余混杂风险，该分析将利用英格兰国民医疗服务体系中早期NSCLC根治性SABR与手术切除使用情况的地理差异。主要结局将是治疗开始后的3年全因死亡率。次要结局将包括3个月、6个月、12个月和24个月的全因和肺癌死亡率、死亡时间、住院次数、增量成本和增量成本效益。
已获得伦敦卫生与热带医学院研究伦理委员会的伦理批准（参考编号29 717 - 1）。研究结果将传播给临床医生、患者、政策制定者和研究人员。
