OBJECTIVES NSCLC patients harboring EGFR mutation invariably developed resistance to EGFR TKI. We postulated that oligoresidual disease (ORD) after initial TKI might harbor resistant clones. This study aimed to test if preemptive local ablative therapy (LAT) can improve progression free survival (PFS) or not compared to historic data. MATERIALS AND METHODS Patients indicated for EGFR TKI who possessed ORD (≤ 4 PET-avid lesions) after an initial 3-month TKI therapy were enrolled. After screening PET-CT, eligible patients with PET-avid ORDs were treated by LAT, either by stereotactic ablative radiotherapy (SABR) or surgery per clinicians' discretion. TKI was continued after LAT until it was considered ineffective. PET-CT was repeated on the 3rd and 12th month post-LAT (or at progression) apart from regular imaging. Further LAT was allowed in oligoprogressive disease. Primary endpoint was PFS rate at one-year from enrollment. Overall survival (OS), PFS and treatment safety were secondary endpoints. A post hoc comparison with screen failure cohort was performed. RESULTS Eighteen patients were enrolled from 2014-17. Recruitment was stopped before the planned number (34) due to slow accrual. Two were excluded due to consent withdrawal and significant protocol violation. Median follow up was 39.1 months. Among the 16 analyzed patients, the one-year PFS rate (i.e. 15 month post TKI) was 68.8 %. Median OS was 43.3 months. All LAT were done by SABR, and none experienced ≥ grade 3 SABR related toxicities. Compared with screen failure cohort (n = 48), pre-emptive LAT effectively reduced risk of progression (HR 0.41, p = 0.0097). CONCLUSION Preemptive LAT in ORD appeared to be safe and feasible. The 1-year PFS rate was encouraging. However, potential biases and the limitations of the study should not be overlooked. Further randomized studies are warranted.

中文翻译：

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ATOM：一项II期研究，评估先发性局部消融治疗对EGFR TKI后NSCLC残留低聚转移的疗效。

目的携带EGFR突变的NSCLC患者总是对EGFR TKI产生抗药性。我们推测，最初的TKI后的少尿症（ORD）可能带有抗性克隆。这项研究旨在测试先发性局部消融治疗（LAT）是否可以改善无进展生存期（PFS），还是不能与历史数据进行比较。材料和方法招募了在最初的3个月TKI治疗后具有ORD（≤4 PET病变）的EGFR TKI患者。筛查PET-CT后，根据临床医师的判断，通过立体定向消融放疗（SABR）或手术，通过LAT治疗符合条件的PET-avid ORD患者。LAT后继续进行TKI，直到被认为无效为止。除常规成像外，在LAT后第3和第12个月（或进展时）重复进行PET-CT。进行性低进展性疾病可允许进一步的LAT。主要终点是入学一年后的PFS率。次要终点是总生存期（OS），PFS和治疗安全性。对筛查失败队列进行事后比较。结果2014-17年共收治18例患者。由于进度缓慢，在计划的人数（34）之前停止了招聘。由于同意撤回和严重违反协议，将其中两名排除在外。中位随访时间为39.1个月。在分析的16名患者中，一年PFS率（即TKI后15个月）为68.8％。中位操作系统为43.3个月。所有LAT均由SABR进行，没有一个经历过≥3级SABR相关毒性。与筛查失败队列（n = 48）相比，先发性LAT有效降低了进展风险（HR 0.41，p = 0.0097）。结论ORD中的抢先LAT似乎是安全可行的。1年PFS率令人鼓舞。但是，潜在的偏见和研究的局限性不容忽视。有必要进行进一步的随机研究。