Differential role of residual metabolic tumor volume in patients with inoperable stage III NSCLC after chemoradiotherapy ± immune checkpoint inhibition.

Abstract

e20558 Background: PET-derived metabolic-tumor-volume (MTV) has shown to be an independent prognosticator in non-small cell lung cancer (NSCLC) patients treated with chemoradiotherapy (CRT). We analysed the prognostic value of residual MTV after completion of thoracic irradiation (TRT) in inoperable stage III NSCLC patients treated with CRT with and without immune check-point inhibition (ICI). Methods: Fifty-six inoperable stage III NSCLC patients (16 female, median age: 65 years) underwent 18F-FDG PET/CT at the same institution before and after completion of CRT. MTV was delineated on 18F-FDG PET/CT using a standard threshold (hepatic SUVmean + 2 x standard-deviation). Patients were divided in volumetric subgroups using median split dichotomization (residual MTV ≤4.0 ml & > 4.0 ml). Residual MTV, clinical features and ICI maintenance (RCT-IO; 21/56 (37.5%) patients) were correlated with clinical outcome (progression-free survival (PFS), local PFS (LPFS), metastasis-free survival (MFS), and overall survival (OS). Results: Median follow-up was 52.0 months. 52 (93%) patients were treated with CRT, 12 (21%) patients with CRT followed by durvalumab, and 9 (16%) patients treated with CRT plus nivolumab (concurrent and sequential). In the entire cohort, smaller residual MTV was associated with longer PFS (median 29.3 vs. 10.5 months, p = 0.015); PFS in patients treated with CRT and ICI was also significantly longer compared to the CRT-only subgroup (median 29.3 vs. 11.2 months, p = 0.010). However, residual MTV was predictive for longer PFS in CRT-only (median 33.5 vs. 8.6 months, p = 0.001), but not in the CRT-ICI patients (p = 0.909). Analogously, patients with smaller MTV had a longer LPFS (median 49.9 vs. 16.3 months, p = 0.002); CRT-ICI patients showed a significantly longer LPFS compared to CRT-only patients (median not reached vs. 16.9 months, p = 0.016). Residual MTV remained a significant prognosticator for LPFS in the CRT-only (median 49.9 vs. 10.1 months, p = 0.01), but not in CRT-ICI patients (p = 0.291). Again, smaller residual MTV remained a significant prognosticator for OS in the CRT-only subgroup (median 63.0 vs. 16.3 months, p = 0.004), but not in CRT-ICI patients (p = 0.720). Even in patients with larger residual MTV, the application of ICI significantly improved OS compared to CRT-only subgroup (median not reached vs. 22.9 months, p = 0.004). Conclusions: Smaller residual MTV is associated with superior clinical outcome in inoperable stage III NSCLC, especially in patients undergoing CRT-only. In contrast, in patients undergoing concurrent or sequential consolidation clinical outcome was independent of residual MTV. Hence, even patients with extensive residual MTV might significantly profit from ICI consolidation.