Metabolic tumor volume on 18F-FDG uptake as a negative predictor after ipilimumab plus nivolumab in advanced non-small cell lung cancer.

Background: Nivolumab plus ipilimumab (Nivo-Ipi) is a standard treatments for metastatic or recurrent non-small cell lung cancer (NSCLC). Unlike programmed death-1 (PD-1) inhibitor monotherapy, the possible predictors of Nivo-Ipi treatment effectiveness remain unclear. Therefore, this retrospective study evaluated the prognostic relevance of 2-deoxy-2-[fluorine-18]-fluoro-d-glucose positron emission tomography (¹⁸F-FDG PET) after Nivo-Ipi treatment in patients with advanced NSCLC.

Methods: Among 130 eligible patients with metastatic or recurrent NSCLC who received Nivo-Ipi as initial treatment and underwent ¹⁸F-FDG PET prior to the initial treatment, the maximum standardized uptake value (SUV_max), SUV_peak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on ¹⁸F-FDG uptake were evaluated.

Results: High MTV and TLG on ¹⁸F-FDG uptake were significantly associated with poor performance status (PS), no response, high neutrophil-to-leukocyte ratio (NLR), low albumin levels, and high C-reactive protein (CRP) level, while SUV_max and SUV_peak showed no significant associations. Univariate analysis of all patients identified PS, bone metastases, NLR, MTV, and TLG as significant predictors of prognosis. By multivariate analysis, NLR and MTV were identified as independent predictors of prognosis. Sub-analysis based on histology and programmed death ligand-1 (PD-L1) expression identified MTV as an independent prognostic predictor for Nivo-Ipi treatment in patients with histological findings of adenocarcinoma (AC) and PD-L1 <1%. A high MTV with poor outcome was closely associated with a poor PS, lymph node metastases, bone metastases, high NLR, low albumin levels, and high CRP level.

Conclusions: MTV determined based on ¹⁸F-FDG uptake was a negative prognostic factor after Nivo-Ipi treatment, particularly in patients with histological findings of AC or PD-L1 <1%.