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. 2018 Aug 6;7(11):e1457598. doi: 10.1080/2162402X.2018.1457598

Table 3.

ANOVA to compare log cytokine levels between pathological complete response (pCR) groups, for both treatment arms, as well as within each arm separately, across four time-points. Cytokines with FDR-adjusted p-value<0.1 in the global three-way ANOVA with time points, treatment arm and treatment response as factors (and TNF-alpha in addition) are highlighted. Only these highlighted cytokines are investigated further in subgroup and post-hoc tests, if the ANOVA F-test for pCR in both arms was significant (p<0.05).

      Post-hoc p-values*
   Post-hoc p-values*
 Global three way ANOVA
Cytokines ANOVA P-value pCR in both arms ANOVA pCR Chemotherapy-only arm 0 W 12 W 25 W 31 W ANOVA pCR Combination (+Bev) arm 0 W 12 W 25 W 31 W Raw p-valuea FDR-adjusted p-valueb
IL1B 0.044                     0.503 0.679
IL1-RA 0.077                     0.539 0.693
IL2 0.109                     0.062 0.152
IL4 0.003 0.402         0.021 0.3 0.028 0.053 0.27 0.025 0.075
IL5 0.001 0.205         0.012 0.6 0.151 0.055 0.14 0.013 0.044
IL6 0.137                     0.716 0.773
IL7 0.072                     0.079 0.178
IL8 0.136                     0.487 0.679
IL9 0.13                     0.343 0.579
IL10 0.039 0.405         0.31         0.006 0.023
IL12 (P70) <0.001 0.202         0.45         <0.001 <0.001
IL13 0.059                     0.255 0.492
IL15 0.569                     0.955 0.955
IL17-A 0.031 0.539         0.022 0.7 0.067 0.19 0.12 0.037 0.1
Eotaxin (CCL11) 0.034                     0.131 0.272
FGF-basic 0.093                     0.485 0.679
G-CSF (CSF3) 0.002 0.419         0.12         0.004 0.022
GM-CSF (CSF2) 0.233                     0.649 0.762
IFN-gamma <0.001 0.154         0.003 0.6 0.038 0.086 0.08 0.006 0.023
IP10 (CXCL10) 0.006 0.014 0.1 0.037 0.33 0.6 0.725         <0.001 <0.001
MCP-1 (CCL2) 0.366                     0.627 0.762
MIP-1a (CCL3) 0.011                     0.317 0.571
MIP-Ib (CCL4) 0.127                     0.706 0.773
PDGF-bb 0.529                     <0.001 <0.001
RANTES (CCL5) 0.565                     0.931 0.955
TNF-alpha 0.008 0.289         0.006 0.6 0.027 0.046 0.22 0.447 0.679
VEGF-A 0.006 0.358 0.7 0.158 0.86 0.033 0.034 0.9 0.015 0.103 0.21 0.003 0.02
*

Post-hoc t-tests for pairwise comparisons with multiple testing adjusted by Bonferroni; performed only if ANOVA P<0.05 (and if global three-way ANOVA FDR-adjusted p<0.1, or if TNF-alpha). W = week.

a

Global F-test in three-way ANOVA with treatment (2 levels), timepoint (4 levels) and treatment response (2 levels) as fixed factors.

b

FDR-adjustment with the method of Benjamini-Hochberg.