Early FMISO PET changes as exploratory predictors of immune checkpoint inhibitor response in advanced lung cancer: a...

¹⁸F-fluoromisonidazole (FMISO) is a positron emission tomography (PET) tracer used to detect tumor hypoxia. Although FMISO PET has been investigated in several experimental and early clinical studies, its utility for monitoring early treatment responses to immune checkpoint inhibitors (ICIs) remains unclear. Because hypoxia modulates the immunosuppressive tumor microenvironment, this pilot study evaluated whether changes in FMISO uptake before and after ICI initiation could serve as an exploratory predictor of treatment response in patients with advanced non-small cell lung cancer (NSCLC). Seventeen patients with advanced NSCLC who received nivolumab plus ipilimumab (Nivo-Ipi) were enrolled. FMISO PET was performed at baseline and at 9 weeks after treatment initiation. Baseline tumor samples were assessed for CD4, CD8, FOXP3, and PD-L1 expression using standard immunohistochemical procedures. The objective response rate was 52.9%. The median baseline FMISO SUV_max and SUV_peak were 2.7 (range, 1.3-4.8) and 2.5 (range, 1.2-4.5), respectively. Patients who showed a ≥ 20% decrease in FMISO SUV after Nivo-Ipi demonstrated a 77.8% probability of achieving a partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST). FMISO uptake was significantly correlated with 2-deoxy-2-[¹⁸F] fluoro-D-glucose accumulation, tumor cell proliferation markers, prealbumin levels, tumor PD-L1, and stromal CD4 expression. When exploratory partial metabolic response (PMR) criteria of a ≥ 20% or ≥ 10% decrease in FMISO SUV were applied, progression-free survival differed significantly between PMR and non-PMR groups, whereas overall survival did not differ significantly. FMISO PET may serve as an exploratory tool for assessing early treatment response to ICIs in patients with advanced NSCLC. However, further studies are required to validate these findings.