First-site-metastasis Pattern in Patients with Inoperable Stage III NSCLC Treated with Concurrent Chemoradiotherapy with or Without Immune Check-Point Inhibition: a Retrospective Analysis

Purpose The aim of this study was to investigate a first-site-metastasis pattern (FSMP) in unresectable stage III NSCLC after concurrent chemoradiotherapy (cCRT) with or without immune checkpoint inhibition (ICI). Methods We defined three patient subgroups according to the year of initial multimodal treatment: A (2011–2014), B (2015–2017) and C (2018–2020). Different treatment-related parameters were analyzed. Observed outcome parameters were brain metastasis-free survival (BMFS), extracranial distant metastasis-free survival (ecDMFS) and distant metastasis-free survival (DMFS). Results 136 patients treated between 2011 and 2020 were included with ≥ 60.0 Gy total dose and concurrent chemotherapy (cCRT); thirty-six (26%) received ICI. Median follow-up was 49.7 (range:0.7–126.1), median OS 31.2 (95% CI:16.4–30.3) months (23.4 for non-ICI vs not reached for ICI patients, p = 0.001). Median BMFS/ecDMFS/DMFS in subgroups A, B and C was 14.9/16.3/14.7 months, 20.6/12.9/12.7 months and not reached (NR)/NR/36.4 months ( p = 0.004/0.001/0.016). For cCRT+ICI median BMFS was 53.1 vs. 19.1 months for cCRT alone ( p = 0.005). Median ecDMFS achieved 55.2 vs. 17.9 ( p = 0.003) and median DMFS 29.5 (95% CI: 1.4–57.6) vs 14.93 (95% CI:10.8–19.0) months ( p = 0.031), respectively. Multivariate analysis showed that age over 65 (HR:1.629; p = 0.036), GTV ≥ 78 cc (HR: 2.100; p = 0.002) and V20 ≥ 30 (HR: 2.400; p = 0.002) were negative prognosticators for BMFS and GTV ≥ 78 cc for ecDMFS (HR: 1.739; p = 0.027). After onset of brain metastasis (BM), patients survived 13.3 (95% CI: 6.4–20.2) months and 8.6 months (95% CI: 1.6–15.5) after extracranial-distant-metastasis (ecDM). Patients with ecDM as FSMP reached significantly worse overall survival of 22.1 (range:14.4–29.8) vs. 40.1 (range:18.7–61.3) months ( p = 0.034) in the rest of cohort. In contrast, BM as FSMP had no impact on OS. Conclusion This retrospective analysis of inoperable stage III NSCLC patients revealed that age over 65, V20 ≥ 30 and GTV ≥ 78 cc were prognosticators for BMFS and GTV ≥ 78 cc for ecDMFS. ICI treatment led to a significant improvement of BMFS, ecDMFS and DMFS. ecDM as FSMP was associated with significant deterioration of OS, whereas BM as FSMP was not.