Serum Inflammatory Dynamics as Novel Biomarkers for Immune Checkpoint Inhibitors in Non-small-cell Lung Cancer With Bone Metastases.

Background/aim: The aim of the study was to develop a novel predictive scoring system based on the dynamics of serum inflammatory indicators in immune checkpoint inhibitor (ICI) treatment on non-small-cell lung cancer (NSCLC) with bone metastases.

Patients And Methods: Sixty patients with NSCLC and bone metastases treated with ICIs between January 2016 and March 2021 were included in the development cohort. Serum neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) levels were assessed before (pre-value) and 6 weeks after (post-value) ICI treatment, and a novel predictive score was developed: pre-value ≥ post-value, 0 points; pre-value < post-value, 1 point; total score: 0-2 points. The associations of these dynamics and the score with clinical outcomes, including overall survival (OS), progression-free survival (PFS), response rate (RR) of bone metastases, and disease control rate (DCR), were evaluated. Furthermore, cross-validation was performed with 23 patients after April 2021 using the same inclusion criteria.

Results: The patients with decreased serum inflammation levels had significantly better OS, PFS, and RR than those with increased levels. Applying the developed score to the development cohort, the patients with 0 points had significantly better OS, PFS, and RR than others. In multivariable analysis, the score independently predicted treatment response to ICI for bone metastasis and prognosis. Cross-validation showed that OS, PFS, and RR were significantly better in the patients in the 0-point group.

Conclusion: The early NLR and CRP dynamics were associated with therapeutic responses to ICIs in NSCLC with bone metastases. Our novel scoring system based on these dynamics is simple and has a high predictive accuracy.