Untangling inter- and intra- tumor heterogeneity functional to clinical decision-making represents an unmet need of the actual Immune checkpoint inhibitors (ICIs)-driven treatment landscape. Multidimensional interrogation of circulating parameters may complement radiomics to non-invasively provide clinically suitable biomarkers. Thus, we aimed at integrating blood hallmarks of systemic inflammation (SI) with high-throughput CT imaging features to develop a predictive model in ICI treated advanced NSCLC.
A cohort of NSCLC patients undergoing ICIs was investigated (n=117). Baseline CT scans and peripheral blood (PB) samples served as a source of, respectively, radiomic features (RFs) and SI indices including derived Neutrophil-to-Lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH). Primary endpoint was the response to ICIs per RECIST. To this end, a Monte Carlo cross-validation exploiting feature selection and logistic regression was used to uncover informative RFs. These RFs together with SI descriptors and a subset of clinical features were mined through an ad hoc genetic algorithm to maximize the classifier accuracy. The discriminative ability of the resulting top 20 selected features was assessed by Kaplan Meier and log-rank tests.
We enrolled 117 advanced NSCLC treated with ICIs as Ist (11%) or IInd or more line (89%). Median OS was 7.8 (95%CI, 5.4-12.8) and PFS 2.5 months (95% CI, 1.1-3.9). According to RECIST criteria, 35% (n:41) were responders (R) while 76 patients belonged to non responders (NR). Using a leave-one-out cross-validation approach we assessed a baseline efficiency of PB-SI (AUC = 0.71). Strikingly, our classifier, including PB-SI and 18 RFs, was significantly associated with clinical response, reaching high performances especially in terms of AUC (AUC = 0.91). Importantly, NSCLC patients classified as NR according to our blood-radiomics predictor displayed a significantly worse OS (median OS 4.1 months, 95% CI, 3.6-6.4) compared to responders (median OS not reached).
Blood-derived pro-inflammatory markers and CT-based RFs may enclose a highly predictive classifier of ICI response in NSCLC affording the non-invasive interception of tumor-immune interactions.
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All authors have declared no conflicts of interest.