Role of Radiosurgery and Stereotactic Ablative Radiotherapy for Oligometastatic Non-Oncogene Addicted NSCLC

SIMPLE SUMMARY: The definition and management of oligometastatic NSCLC have been incorporated into current guidelines on lung cancer, supporting the use of a definitive treatment with curative intent, including the focal ablation of all sites of oligometastatic involvement. Clinical evidence highlighting the use of local ablative treatment (LAT), alone or in combination with systemic therapies, demonstrated significant benefit in local control and progression-free survival, especially in “oncogene-addicted” patients, who benefit the most from the local treatment of oligoprogressive or oligorecurrent sites to restore the overall sensitivity of the metastatic disease to target therapies. On the other hand, only a few studies, with limited numbers, focused specifically on “non-oncogene” addicted patients. The aim of this study is to assess the role of LAT, referred to stereotactic ablative radiotherapy, and to report clinical outcomes of the largest retrospective series, to date, of patients with oligometastatic EGFR/ALK/ROS1 wild type NSCLC. ABSTRACT: Local ablative therapy (LAT), intended as stereotactic ablative radiotherapy or stereotactic radiosurgery, is a well-recognized effective treatment for selected patients with oligometastatic NSCLC. Current clinical evidence supports LAT alone or in combination with systemic therapies. Our retrospective mono-institutional study aims to assess the role of LAT with a peculiar focus on the largest series of non-oncogene addicted oligometastatic NSCLC patients to date. We included in this analysis all patients with the mentioned disease characteristics who underwent LAT for intracranial and/or extracranial metastases between 2011 and 2020. The main endpoints were local control (LC), progression free survival (PFS) and overall survival (OS) in the whole population and after stratification for prognostic factors. We identified a series of 245 consecutive patients (314 lesions), included in this analysis (median age 69 years). In 77% of patients, a single metastasis was treated with LAT and intracranial involvement was the most frequent indication (53% of patients) in our series. The overall response rate (ORR) after LAT was 95%. In case of disease progression, 66 patients underwent new local treatments with curative intent. With a median follow-up of 18 months, median PFS was 13 months (1-year PFS 50%) and median OS was 32 months (1-year OS 75%). The median LC was not reached (1-year LC 89%). The presence of brain metastases was the only factor that negatively affected all clinical endpoints, with a 1-year LC, PFS and OS of 82%, 29% and 62% respectively, compared to 95%, 73% and 91%, respectively, for patients without BMs (p < 0.001 for each endpoint). At the multivariate analysis, mediastinal nodal involvement at baseline (p = 0.049), ECOG PS = 1 (p = 0.011), intracranial disease involvement (p = 0.001), administration of chemotherapy in combination with LAT (p = 0.020), and no delivery of further local treatment for progression or delivery of focal treatment for intracranial progression (p < 0.001) were related to a poorer OS. In our retrospective series, which is to our knowledge the largest to date, LAT showed encouraging results and confirmed the safety and effectiveness of focal treatments in non-oncogene addicted oligometastatic NSCLC patients.