立体定向消融体部放疗放射治疗(stereotactic ablative body radiotherapy ，SABR）被广泛用于治疗不能手术的I期非小细胞肺癌（NSCLC）， 与标准放疗相比 ，目前没有前瞻性证据表明，这种治疗方法可改善局部控制或延长总体生存期。 我们的目的是比较两种治疗技术。
此多中心、III期、随机对照试验在澳大利亚的11家医院和新西兰的3家医院进行。入组患者为18岁以上，经18F-氟脱氧葡萄糖PET确诊为I期(T1-T2aN0M0) NSCLC， 在医学上无法手术或拒绝手术，则符合条件。依照美国东部肿瘤协作组(ECOG)体力状况评分为0或1， 并且肿瘤必须位于外周 。基于T分期对患者进行分层，之后按照2:1的比例随机接受SABR[如果肿瘤距离胸壁< 2厘米，54Gy(18Gy×3次)，或48(12Gy×4次)]，或标准放疗(66 Gy /33次或50 Gy/ 20次)。主要终点是局部治疗失败的时间（根据实体肿瘤1.0版中的反应评估标准评估），假设SABR与标准放疗相比将导致更好的局部控制。所有功效分析均基于意向治疗分析。根据患者实际接受的治疗，在每个方案的基础上进行安全性分析， 假设SABR与标准放疗相比将导致更好的局部控制。
2009年12月31日至2015年6月22日， 101名符合条件的患者入选并随机分配接受SABR（n = 66）或标准放疗（n = 35） 。SABR组5例(7.6%)、标准放疗组2例(6.5%)未接受治疗，两组各有4例在研究结束前退出。截止2017年7月31日，标准放疗组局部治疗失败的中位随访为2.1年(IQR 1.2 – 3.6)，SABR组中位随访为2.6年(IQR 1.6 – 3.6)。101例患者中有20例(20%)局部进展：SABR组66例患者中有9例（14％），标准放疗组35例患者中11例（31％），与标准放疗组相比，SABR组的局部治疗失败率得到改善（风险比0.32,95％CI 0.13-0.77,p = 0.0077）。两组均未达到局部治疗失败的中位时间。在接受SABR治疗的患者中，治疗相关4级不良事件1例(呼吸困难)，3级不良事件7例(咳嗽2例、缺氧1例、肺部感染1例、体重减轻1例、呼吸困难1例、疲劳1例)；标准治疗组发生2例3级不良事件(胸痛)。
对于无法手术的I期周围型非小细胞肺癌患者(peripherally located stage 1 NSCLC)，与标准放疗相比，SABR能更好地控制原发性疾病。本试验的结果表明，SABR应是这一患者群体的首选治疗方法。
Stereotactic ablative body radiotherapy (SABR) is widely used to treat inoperable stage 1 non-small-cell lung cancer (NSCLC), despite the absence of prospective evidence that this type of treatment improves local control or prolongs overall survival compared with standard radiotherapy. We aimed to compare the two treatment techniques.
We did this multicentre, phase 3, randomised, controlled trial in 11 hospitals in Australia and three hospitals in New Zealand. Patients were eligible if they were aged 18 years or older, had biopsy-confirmed stage 1 (T1–T2aN0M0) NSCLC diagnosed on the basis of 18F-fluorodeoxyglucose PET, and were medically inoperable or had refused surgery. Patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1, and the tumour had to be peripherally located. Patients were randomly assigned after stratification for T stage and operability in a 2:1 ratio to SABR (54 Gy in three 18 Gy fractions, or 48 Gy in four 12 Gy fractions if the tumour was <2 cm from the chest wall) or standard radiotherapy (66 Gy in 33 daily 2 Gy fractions or 50 Gy in 20 daily 2·5 Gy fractions, depending on institutional preference) using minimisation, so no sequence was pre-generated. Clinicians, patients, and data managers had no previous knowledge of the treatment group to which patients would be assigned; however, the treatment assignment was subsequently open label (because of the nature of the interventions). The primary endpoint was time to local treatment failure (assessed according to Response Evaluation Criteria in Solid Tumors version 1.0), with the hypothesis that SABR would result in superior local control compared with standard radiotherapy. All efficacy analyses were based on the intention-to-treat analysis. Safety analyses were done on a per-protocol basis, according to treatment that the patients actually received. The trial is registered with ClinicalTrials.gov ( NCT01014130) and the Australia and New Zealand Clinical Trials Registry (ACTRN12610000479000). The trial is closed to new participants.
Between Dec 31, 2009, and June 22, 2015, 101 eligible patients were enrolled and randomly assigned to receive SABR (n=66) or standard radiotherapy (n=35). Five (7·6%) patients in the SABR group and two (6·5%) in the standard radiotherapy group did not receive treatment, and a further four in each group withdrew before study end. As of data cutoff (July 31, 2017), median follow-up for local treatment failure was 2·1 years (IQR 1·2–3·6) for patients randomly assigned to standard radiotherapy and 2·6 years (IQR 1·6–3·6) for patients assigned to SABR. 20 (20%) of 101 patients had progressed locally: nine (14%) of 66 patients in the SABR group and 11 (31%) of 35 patients in the standard radiotherapy group, and freedom from local treatment failure was improved in the SABR group compared with the standard radiotherapy group (hazard ratio 0·32, 95% CI 0·13–0·77, p=0·0077). Median time to local treatment failure was not reached in either group. In patients treated with SABR, there was one grade 4 adverse event (dyspnoea) and seven grade 3 adverse events (two cough, one hypoxia, one lung infection, one weight loss, one dyspnoea, and one fatigue) related to treatment compared with two grade 3 events (chest pain) in the standard treatment group.
In patients with inoperable peripherally located stage 1 NSCLC, compared with standard radiotherapy, SABR resulted in superior local control of the primary disease without an increase in major toxicity. The findings of this trial suggest that SABR should be the treatment of choice for this patient group.
The Radiation and Optometry Section of the Australian Government Department of Health with the assistance of Cancer Australia, and the Cancer Society of New Zealand and the Cancer Research Trust New Zealand (formerly Genesis Oncology Trust).