Bombarding Oligoprogression: Oncologic Outcomes Following Localized Radiotherapy in Oligoprogressive Non-Small Cell Lung Cancer Patients on Maintenance Systemic Therapy

Abstract

<h3>Purpose/Objective(s)</h3> The purpose of this study is to evaluate the efficacy and toxicity of focal radiotherapy (RT) to all oligoprogressive sites to prolong the durability of current systemic therapy or meaningful clinical benefit (MCB) in patients with metastatic non-small cell lung cancer (NSCLC) and one to five sites of progressive disease. The primary endpoints include progression-free survival (PFS) and MCB. Secondary endpoints include overall survival (OS), local control (LC), event free survival (EFS), and toxicities of RT. <h3>Materials/Methods</h3> Treatment records at our institution were reviewed (2018 to 2021) and included if they had metastatic NSCLC, started maintenance systemic therapy, developed oligoprogression (1-5 sites), and all oligoprogressive sites amenable to and treated with RT with the intent for MCB. Prior RT was allowed. Kaplan-Meier survival analysis and log-rank testing were performed using R-Studio software. PD-L1 status and actionable mutations were also documented. Toxicities were documented using the CTCAE v5.0. <h3>Results</h3> From our records, 23 patients were identified and met inclusion criteria. Thirteen (57%) were female and 10 were male. Twenty-one (91%) of patients had adenocarcinoma, 10 (43%) had actionable mutations, and 13 (57%) had PD-L1 expression > 1%. 13 patients (56%) were on PD1/PD-L1 checkpoint inhibition, 7 (30%) patients were on EGFR-targeted therapy, and 3 (13%) patients were receiving chemotherapy alone. A total of 41 targets were irradiated with a median of 2 per patient (range 1 to 4), with 28 (68%) targets receiving stereotactic body radiotherapy or radiosurgery, 12 (29%) receiving intensity-modulated radiotherapy, and 1 (2%) receiving 3D conformal RT. At a median follow-up of 12.6 months, there were 17 progression events; 6 patients started next-line therapy and 6 were recommended no further therapy based on declining performance status or no suitable next line systemic therapy. Four patients received additional targeted radiotherapy for oligoprogression and did not switch therapies. Median PFS, OS, and EFS were 8.4 months (IQR 4.1 – 17.5), 17.2 months (IQR 12.6 – 31.4), and 8.3 months (IQR 2.7 – 12.0), respectively. At 12 months follow-up, 6 (43%) of 14 living patients maintained their systemic therapy without initiating next-line therapy. Median time to start of next line therapy (MCB) was not reached in this analysis due to few events. There was one local failure of an irradiated site yielding an in-field failure rate of 4%. Two patients (9%) had grade 3 chronic toxicity related to RT and were medically managed. <h3>Conclusion</h3> We identified that in oligoprogressive metastatic NSCLC patients, targeted RT to all progressive sites yielded high rates of LC and favorable rates of PFS and MCB. Future prospective trials with well-selected oligoprogressive patients are warranted to further evaluate the role of focal RT to oligoprogressive sites in this patient population.