The Radiotherapeutic Factors Associated with Reduced Risk of Progression in Patients with Oligometastatic Non-Small Cell Lung Cancer Treated with Local Ablative Radiotherapy

Abstract

<h3>Purpose/Objective(s)</h3> We aimed to investigate which subset of patients with oligometastatic lung adenocarcinoma would benefit from local ablative radiotherapy (LART). <h3>Materials/Methods</h3> 274 patients diagnosed with stage IV non-small cell lung cancer (NSCLC), with three or fewer metastases at the timing of LART were enrolled. Histology other than adenocarcinoma (n=56), patients who did not undergo systemic therapy (n=23) at the time of RT, who had uncontrolled brain metastases (n=20) were excluded. Thus, a total of 175 patients were included. Among these patients, some patients received LART as 1^st line treatment and were defined as the oligometastasis group. The rest of the patients received LART when presented with oligoprogression in spite of other treatments. We classified these patients as the olioprogression group. Single-fraction cumulative doses ≥ 12 Gy, 3-fraction doses ≥ 24 Gy, 5-fraction doses ≥ 30 Gy were regarded as LART. The primary end point was progression-free survival (PFS); secondary end point was overall survival (OS). <h3>Results</h3> In the oligometastasis group (N=53), 25 patients (47.2%) presented with EGFR mutation, 4 patients (7.5%) with ALK positive status and 9 patients (17.0%) with ROS1. Thirty-seven patients (69.8%) had single metastatic lesions, and 12 patients (22.6%) had two lesions. Bone metastasis was the most commonly treated site (63.0%) followed by lung (27.8%). Among these patients, 38 patients (71.7%) received LART to all sites of gross disease, and we defined it as all metastatic site RT. The median follow-up time was 20.2 months (range, 0.3-109.7 months). During this follow-up period, 1-year PFS was 39.9% and 3-year PFS was 22.4%. In a Cox multivariate model, EGFR and ALK positive status were independently correlated with improved PFS (hazard ratio (HR), 0.24; 95% confidence interval (CI), 0.11-0.56, HR, 0.04; 95% CI, 0.01-0.37, respectively). All metastatic site RT independently correlated with PFS (HR 0.39; 95% CI, 0.18-0.86). In patients who were administered with Tyrosine kinase inhibitor (TKI) at the time of RT (N=23) and treated with all metastatic site RT, 1-yr PFS was 86.7%, while that of the patients who were not treated with all site RT was 37.5% (p=0.029). In the oligoprogression group (N=122), 62 patients (50.8%) were treated with TKI, 45 patients (36.9%) with cytotoxic CTx for 1^st line systemic therapy. At the time of LART, 50 patients (41.0%) were undergoing TKI and 43 patients (35.2%) immunotherapy. 67.2% of the patients (N=82) maintained the CTx regimen after LART. The median duration prolonged was 5.8 months. In the subset of patients who were treated with TKI at the time of LART, the median duration prolonged was 11.1 months. <h3>Conclusion</h3> EGFR positive and ALK positive status are associated with improved PFS in patients with oligometastatic lung adenocarcinoma. For oligometastatic patients, early all site RT might improve PFS, especially for those who are receiving TKI. In patients who presented with oligoprogression, LART could delay the timing of CTx regimen change.