Oligoprogressive Metastatic Lung Cancer Treated with Definitive Radiotherapy Without a Change in Systemic Therapy

In patients with metastatic non-small cell lung cancer (NSCLC) who have objective radiographic progression, initiation of new systemic therapy is the next therapeutic step. However, in selected cases with limited disease progression, local radiotherapy (RT) may allow for elimination of resistant tumor clones and the continuation of otherwise effective systemic therapy. In this study, we hypothesize that definitive RT would be an effective tool to delay a change in therapy in a large cohort of oligoprogressive (OPG) NSCLC patients. Patients with metastatic NSCLC treated with definitive RT at a single tertiary academic center between 2008-2019 were identified. Inclusion criteria were as follows: 1) pathological diagnosis of metastatic NSCLC, 2) ≤ 3 sites of intracranial or extracranial OPG, and 3) receipt of definitive RT to all sites of isolated progression without a change in systemic therapy. Radiographic PFS (rPFS: time to first evidence of new disease on CT) and clinical PFS (cPFS: time to change in therapy due to disease progression) were calculated. Associations of clinical characteristics with rPFS and cPFS were assessed using univariate and multivariate Cox proportional hazards models. A total of 198 unique patients with 253 OPG events treated with definitive RT were identified. Median follow up time was 14.9 months (range: 0.4–128.4). There was equal representation of intracranial (51.4%) and extracranial (48.6%) OPG events. The median age was 66 years (range: 33-91), 57.6% were female, and 72.7% were Caucasian. Most patients had adenocarcinoma (80.2%), N2-N3 disease (59.9%), synchronous timing of metastases (55.7%), one site of progression (76.0%), and ≤ 3 metastases at diagnosis (76.7%). Median rPFS and cPFS was 7.9 months (range: 6.5–10.0) and 8.8 months (range: 7.2–10.9), respectively. After adjusting for race, histology, performance status, and significant covariates (p<0.05) in a univariate model, the following variables were associated with decreased risk for radiographic progression: KPS >70 (HR 0.40, p = 0.003), ≤ 3 metastases at diagnosis (HR 0.57, p = 0.03), time to oligoprogression >6 months (HR 0.59, p = 0.009), 0-1 (HR 0.50, p = 0.02) or 2-3 (HR 0.42, p = 0.002) previous systemic therapies, and one site of oligoprogression (HR 0.55, p<0.001). Definitive RT is a feasible treatment option for OPG metastatic NSCLC to delay the initiation of next line therapies. Our outcomes compare favorably to median PFS of systemic therapies alone, which often have poor response rates and efficacy. Further randomized prospective data may help to validate these findings and identify which patients are most likely to benefit.