O2169: Association of serum inflammatory markers and clinical outcomes among children with renal tumors

Background: Elevated pre-treatment inflammatory markers predict disease progression and overall survival among adults with kidney cancer, including elevated neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), platelet count, lymphocyte count, and neutrophil count. We hypothesized elevated inflammatory markers at diagnosis predict adverse cancer related outcomes for children with renal malignancies.

Methods: We performed retrospective chart review of all children with renal malignancy who underwent surgical resection at two children’s hospitals from 2002-2022. Differences in patient demographics and laboratory parameters were compared between overall disease stages using Kruskal-Wallis and chi-squared or Fisher’s exact tests, as appropriate. Differences in tumor characteristics and patient outcomes were compared by elevated LMR, NLR, and PLR at diagnosis using Wilcoxon tests and chi-squared or Fisher’s exact tests, as appropriate. For LMR, NLR, and PLR, optimal cutpoints for predicting overall and local disease ≥ stage 3 were determined using the Youden index for optimization. Analyses were conducted for the overall population and a Wilms tumor subset. Optimal cutpoints were identified using the overall population and applied to the subset. Change in serum markers from diagnosis to off therapy were compared based on tumor histology.

Results: Data were collected from 254 patients (235 Wilms tumor, 6 renal cell carcinoma, 6 clear cell sarcoma, 4 rhabdoid tumor, 3 other tumors). Median age 38.6 months and 48% female; 45 had stage 1 disease, 59 stage 2, 64 stage 3, 60 stage 4, and 26 stage 5 (Table 1). Preoperative inflammatory markers varied with overall stage (Table 2). LMR, NLR, and PLR increased as overall stage increased. Optimal cutpoints for predicting stage 3 or greater disease were 0.21 for LMR (AUC 0.65, sensitivity 71%, specificity 55%), 1.42 for NLR (AUC 0.62, sensitivity 63%, specificity 65%), and 103.7 for PLR (AUC 0.62, sensitivity 64%, specificity 55%). Applying these cutoffs, elevated LMR was associated with higher rates of focal or diffuse anaplasia compared to normal LMR (11.5% vs 1.1%, p< 0.05). Elevated NLR was associated with higher rates of focal or diffuse anaplasia (13.2% vs 1.9%, p< 0.01) and higher mortality (9.2% vs 1.7%, p= < 0.05). Elevated PLR was associated with higher rates of focal or diffuse anaplasia (12.3% vs 1%, p< 0.01) and recurrence (15.7% vs 6.5%, p< 0.05). The same relationships were found among the Wilms tumor subset. There was no statistically significant relationship between elevation of inflammatory ratios and inflammation, fibrosis, inflammatory pseudocapsule, or lymphocytic infiltrate on final pathology report. There was no difference in absolute or percent change in NLR, PLR, or LMR from diagnosis to off therapy between patients with favorable or unfavorable histology.

Conclusion: Elevation in serum inflammatory markers at diagnosis among children with renal tumors is associated with adverse clinical outcomes and unfavorable histology.