BACKGROUND: Immune checkpoint inhibitors (ICI) benefit only a subset of patients with non-small cell lung cancer (NSCLC). We evaluated whether response patterns differ by metastatic site and whether early radiological change predicts long-term outcomes. METHODS: Patients with advanced NSCLC treated with ICI were prospectively enrolled between 03/2019 - 03/2023. Imaging was assessed blindly by a board-certified radiologist per iRECIST. Early response was defined as change in sum of diameters (SoD) from baseline to first restaging (8-12 weeks). Baseline and early inflammatory laboratory markers were collected. Endpoints were associations of early radiological response with durable clinical benefit (DCB; disease control ≥ 6 months), best overall response (BOR), overall survival (OS), progression-free survival (PFS) and organ-specific tumor burden. RESULTS: Among 122 patients (46% female; median age 65) 32.8% were BOR responders and 47.5% achieved DCB. Median OS was 64.6 weeks and PFS 31.6 weeks. Early SoD reduction predicted DCB (p > 0.05, AUC 0.764) and BOR (p < 0.01, AUC 0.701). Organ-specific effects were seen particularly in lung and lymph nodes (all p ≤ 0.021). First-line ICI showed greater early shrinkage (p < 0.001) and higher response (p = 0.024), later-line therapy reduced response odds (BOR: OR 0.34; DCB: OR 0.38). Although selected baseline inflammatory markers were associated with survival in univariable analyses, neither baseline nor dynamic laboratory parameters retained independent significance in multivariable models after correction for multiple testing. CONCLUSIONS: Specific organ sites show differential sensitivity to ICI, with lung and nodal metastases demonstrating the most pronounced early regression. Early radiological dynamics robustly predicted DCB, BOR, PFS, and OS and outperformed laboratory biomarkers, supporting their use as a practical, clinically relevant tool to identify patients most likely to benefit from ICI. CLINICAL TRIAL NUMBER: Not applicable.
Kleinberger et al. (Fri,) studied this question.