Pattern of first-site failure and salvage treatment in patients with inoperable stage III non-small cell lung cancer after chemoradiotherapy

Abstract

Background: The standard of care treatment for inoperable stage III NSCLC is concurrent chemoradiotherapy (CRT) followed by consolidation with durvalumab. Locoregional and distant recurrences remain common. Herein, we examine pattern of firstsite failure and salvage treatment. Methods: We analysed the medical charts of 99 patients treated with CRT. Scans from date of first-site failure were fused with the delivered treatment plans. Recurrences were identified as in-field recurrence (IFR), out-of-field recurrence (OFR) [outside 50Gy isodose line] and distant metastases (DM). Using the Kaplan-Meier method with logrank test for univariate analysis, the effect of salvage surgery (S), radiotherapy (sRT), chemotherapy (sCT) and immunotherapy (sIO) on overall survival (OS) was evaluated. Results: With a median follow-up of 17.2 months, the mOS for all patients was 20.8 months. 26 patients (26%) with IFR had a mOS of 19.3 months. In patients who survived at least 12 months from initial diagnosis (74%), IFR was a significant negative prognosticator (mOS 19.3 vs 40.0 months; p<0.001). 25 (25%) patients developed OFR with no significant impact on survival (27.1 vs 20.8 months, p=0.313). 3 (12%) patients with OFR underwent salvage surgery (p=0.057) and were still alive at the time of this analysis. 5 (20%) patients underwent sRT with a mOS of 71.2 vs 19.1 months (p=0.014). 13 (52%) patients with OFR received sCT; mOS 26.4 vs 32.7 mo. (p=0.644;) and 4(16%) pts received sIO (mOS: 64.6 vs 26.4 months; p=0.222). Distant and brain relapse were detected in 42 (42%) and 16 (16%) patients; mOS 19.1 vs. 22.9 months (p=0.819) and 19.1 vs 20.8 mo. (p=0.635), respectively. 15 (94%) patients with brain relapse received cranial radiotherapy: 7 (47%) whole brain irradiation and 8 (53%) stereotactic radiosurgery (mOS 15.3 vs. 37.8 mo.; p=0.064). Conclusions: IFR was a significant negative predictor of OS in patients, who survived >1 year after initial diagnosis. Patients with OFR benefit most from salvage operation and/or radiotherapy. Furthermore, we observed survival benefit in patients who received SRS vs. WBRT for brain relapse.