1. Integrated CT imaging and tissue immune features disclose a radio-immune signature with high prognostic impact on surgically resected NSCLC
- Author
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Paolo Pagano, Gianluca Milanese, Bruno Lorusso, Giulia Mazzaschi, Francesca Trentini, Mario Silva, Caterina Frati, Denise Madeddu, Federico Quaini, Marcello Tiseo, Costanza Lagrasta, Angela Falco, Nicola Sverzellati, Roberta Minari, Giovanni Roti, Letizia Gnetti, and Luca Ampollini
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Specific time ,Survival outcome ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,0302 clinical medicine ,Immune system ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Tumor Microenvironment ,medicine ,Humans ,Lung cancer ,Prognostic models ,Tumor-infiltrating lymphocytes ,business.industry ,Prognosis ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Ct imaging ,Tomography, X-Ray Computed ,business ,Validation cohort - Abstract
Qualitative and quantitative CT imaging features might intercept the multifaceted tumor immune microenvironment (TIME), providing a non-invasive approach to design new prognostic models in NSCLC patients.Our study population consisted of 100 surgically resected NSCLC patients among which 31 served as a validation cohort for quantitative image analysis. TIME was classified according to PD-L1 expression and the magnitude of Tumor Infiltrating Lymphocytes (TILs) and further defined as hot or cold by the tissue analysis of effector (CD8-to-CD3Specific CT-SFs (texture [TXT], effect [EFC] and margins [MRG]) strongly correlated to PD-L1 and TILs status and showed significant impact on survival outcome (TXT, HR:3.39, 95 % CI 1.12-10-27, P 0.05; EFC, HR:0.41, 95 % CI 0.18-0.93, P 0.05; MRG, HR:1.93, 95 % CI 0.88-4.25, P = 0.09). Seven CT derived radiomic features were able to sharply discriminate cases with hot (inflamed) vs cold (desert) TIME, which also exhibited opposite OS (long vs short, HR:0.09, 95 % CI 0.04-0.23, P 0.001) and DFS (long vs short, HR:0.31, 95 % CI 0.16-0.58, P 0.001). Moreover, we identified 6 prognostic radiomic features among which ClusterProminence displayed the highest statistical significance (HR:0.13, 95 % CI 0.06-0.31, P 0.001). These findings were independently validated in an additional cohort of NSCLC (HR:0.11, 95 % CI 0.03-0.40, P = 0.001). Finally, in our training cohort we developed a multiparametric prognostic model, interlacing TIME and clinico-pathological characteristics with CT-SFs (ROC curve AUC:0.83, 95 % CI 0.71-0.92, P 0.001) or CT-RFs (AUC: 0.91, 95 % CI 0.83-0.99, P 0.001), which appeared to outperform pTNM staging (AUC: 0.66, 95 % CI 0.51-0.80, P 0.05) in the risk assessment of NSCLC.Higher order CT extracted features associated with specific TIME profiles may reveal a radio-immune signature with prognostic impact on resected NSCLC.
- Published
- 2020