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Letters to the Editor
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Figure 2. Association of survival outcomes with pre-treatment sCD163 levels. (A) Overall survival (OS) and (B) progression-free survival (PFS) according to pre-treatment sCD163 level (< vs. ≥ median, 1,160 ng/mL) in the trial cohort. (C) OS and (D) PFS according to pre-treat- ment sCD163 level (< vs. ≥ median, 2,950 mg/mL) in the population-based cohort.
12.1 (StataCorp LP, Texas, TX, USA). The Wilcoxon signed ranks test was used to evaluate changes in sCD163 levels during treatment. The Mann-Whitney U- test was used to compare sCD163 levels between patient and control groups. Spearman rank analysis was used in correlation analyses. The χ2 test and the Fisher-Freeman- Halton test were used to evaluate differences in frequen- cy of prognostic factors. The Kaplan-Meier method was used to estimate differences in outcome between the subgroups. The degree of significance was calculated using a log-rank test. Cox regression analysis (with 95% confidence intervals [95% CI]) was used and adjusted for gender and the variables in the International Prognostic Index, and in the trial cohort also for molecular subtype. P-values <0.05 were considered statistically significant. All statistical tests were two-tailed.
The baseline characteristics of the patients in the trial cohort are presented in Table 1. The median follow-up for the patients alive was 61 months (range, 40-87). In total, 16 (13%) patients died and 18 (15%) relapsed dur- ing follow-up. Five-year overall survival and progression- free survival rates were 87% and 83%, respectively. Pre- treatment sCD163 levels were higher in these patients than in healthy volunteers (median 1,160 ng/mL [range, 370-3,621] vs. 437 ng/mL [range, 220-518]; P<0.001), and higher in the subgroup with non-germinal center B-cell like (non-GCB) lymphoma than in the GCB subgroup (Table 1, Online Supplementary Figure S1C), declining in response to therapy (median 975 ng/mL [range, 299-
1,923], P<0.001) (Figure 1A, Online Supplementary Figure S1E, G). Pre-treatment sCD163 levels correlated with CD163+ TAM (Figure 1C) and with CD163 mRNA levels (Figure 1D), whereas no correlation was found with blood monocyte counts (ρ=0.0, P=1.00). High pre-treat- ment sCD163 levels (above the median) translated into poor outcome (Figure 2A, B). Relative risks of death and progression were, respectively, 3.4-fold (95% CI: 1.12- 10.51, P=0.031) and 2.7-fold (95% CI: 1.05-6.94, P=0.04) higher. In Cox regression analysis including International Prognostic Index factors, gender and molecular subtype, sCD163 remained the only significant prognostic factor for progression-free survival (hazard ratio [HR]=4.40, 95% CI: 1.09-17.83; P=0.038) (Online Supplementary Table S1). A similar trend was seen for poor overall survival (HR=5.08, 95% CI: 0.98-26.39; P=0.053) (Online Supplementary Table S1). The mean pre-treatment sCD163 levels in patients stratified by their later response to therapy are presented in Online Supplementary Figure S1I.
The baseline characteristics of the population-based cohort are presented in Table 1. During a median follow- up of 40 months (range, 0-94), 42 (34%) patients died and 29 (23%) relapsed. The estimated 5-year overall and progression-free survival rates were 65% and 57%, respectively. The median pre-treatment sCD163 level was 2,950 ng/mL (range, 870-30,000 ng/mL). All cases later developing progressive disease had a diagnostic sCD163 value above the median (Table 1). Pre-treatment
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