1061P Static and dynamic tracking of radiomic and immunophenotypic features predicts the benefit of immune checkpoint inhibitors in advanced NSCLC

Abstract

Parallel monitoring of radiomic and blood/tissue immunophenotypic cues may intercept the critical events implicated in Immune Checkpoint Inhibitors (ICIs) efficacy. Thus, we explored radio-immune features and their evolution to provide suitable predictors of ICI response in advanced NSCLC patients. On 58 ICI treated NSCLC cases, we prospectively evaluated: Tumor Immune Microenvironment (TIME) by PD-L1 expression and incidence and spatial distribution of infiltrating lymphocytes (TILs); peripheral blood (PB) at T0 and first disease assessment (T1) for the quantification of effector (NK, CD8, PD1, Granzyme B [GnzB], Perforin [Perf], Ki67) and suppressor (CD4+CD25+FOXP3+ Tregs) phenotypes (flowcytometry), soluble PD-L1 (sPD-L1) and Lung Immune Prognostic Index (LIPI); CT derived Radiomic Features (RFs, n: 851) at T0 and T1. Changes in PB parameters were expressed as Δ% = ([T1 - T0]/T0)*100, while ΔRFs as (T1-T0)/T0. Primary endpoint was tumor response (RECIST v.1.1): CR/PR or SD ≥ 6 months defined clinical benefit (CB), while SD < 6 months or PD non-responders (NR). Baseline immune profile of CB patients comprised: -TIME enriched of CD3+, CD8+ and PD1+ and poor of immune excluded (IE) TILs (Mann-Whitney, p<0.01 vs NR); -PB bearing prominent effector cells, low sPD-L1 and good LIPI, enclosing a highly prognostic model (Fisher, p<0.005). Among PB-TIME associations, PB Tregs correlated directly with IE and inversely with intratumor-CD8+ TILs (p<0.05). Mean Δ% NK, CD8+Ki67+ and CD8+GnzB/Perf+ were, respectively, -20%, -0.4% and -41% in NR and +22%, +170% and +65% in CB, which also displayed a greater boost of counterregulatory Tregs (p<0.05). Out of 657 ΔRFs resulting from pre-processing and Z-score standardization, 11 were differentially regulated in CB vs NR (Mann Whitney, p<0.05). Distinct ΔRFs principal components, encompassing wavelet-HLL_firstorder_Maximum and -HLL_firstorder_Skewness, showed, respectively, direct and inverse correlation with Δ% CD8+Ki67+ lymphocytes. Static and dynamic radio-immune signatures may discern ICI outcome in advanced NSCLC, ultimately enabling tailored therapeutic approaches.