3650 - Oligoprogression-Directed vs. Consolidative Thoracic Radiotherapy in Stage IV NSCLC: A Single-Institution Retrospective Study

Purpose/Objective(s): Local thoracic radiotherapy in stage IV non-small cell lung cancer (NSCLC) is commonly used as consolidative treatment or for oligoprogression. However, it remains unclear whether consolidation or oligoprogression-directed radiotherapy is associated with superior outcomes. This study compares outcomes between these approaches and explores prognostic factors.

Materials/Methods: We performed a retrospective review of patients with pathologically-confirmed stage IV NSCLC treated at our institution with thoracic radiotherapy between May 2015 and December 2024. Treatments were categorized as either consolidative (CON, delivered immediately before or after first-line induction therapy) or oligoprogression-directed (OLI, targeting thoracic oligoprogression of the primary tumour and/or thoracic lymph nodes). Techniques evaluated included stereotactic body radiotherapy (SBRT, =8 Gy per fraction) or hypofractionated radiotherapy (hypoRT, 3 to <8 Gy per fraction). Demographics, clinical and dosimetric data were collected from electronic health record systems. Local control (LC) was calculated per-treatment from the time of radiotherapy, while overall survival (OS) was calculated per-patient from the time of stage IV diagnosis, as some patients received multiple radiation courses.

Results: 147 patients who received 163 treatments were analyzed, including 70 CON (20 prior to and 50 following systemic therapy) and 93 OLI. Of these treatments, 101 were SBRT and 62 were hypoRT. The median age was 67 years; 82 patients were female and 65 were male. 139 patients had de novo metastatic disease, while 8 had progression of localized disease. Histologies included adenocarcinoma (113) and squamous cell carcinoma (32). 130 patients were active or ex-smokers. Median OS was significantly longer in the OLI group compared to the CON group (51 vs 28 months, P < 0.001, HR = 0.46, 95% CI [0.29, 0.72]). Median LC was not statistically different between groups (83 vs 73 months, P = 0.609, HR = 1.21, 95% CI [0.58, 2.51]), nor was distant failure (35/68 vs 40/78, chi-square P = 0.56). Performance status (ECOG 0-1 vs 2-3) was independently associated with improved OS (P < 0.001, HR = 1.83, 95% CI [1.22, 2.60]). In subgroup analyses, PD-L1 expression = 50% was associated with improved OS in patients treated with hypoRT (P = 0.042, HR = 0.71, 95% CI [0.51, 0.99]) but not SBRT (P = 0.058, HR = 1.37, 95% CI [0.99, 1.90]).

Conclusion: Oligoprogression-directed radiotherapy was associated with longer OS compared to consolidative radiotherapy, with no difference in local control or distant failure. These findings highlight that the timing of radiotherapy in stage IV NSCLC is critical, especially in the context of newer systemic therapies. We aim to evaluate the sequencing of radiotherapy in stage IV NSCLC prospectively through a phase II trial comparing consolidative versus oligoprogression-directed thoracic radiotherapy.