Objectives: 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. Materials and methods: 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-CD3high/PD-1-to-CD8low) or inert (CD8-to-CD3low/PD-1-to-CD8high) phenotypes. CT datasets acted as source for qualitative (semantic, CT-SFs) and quantitative (radiomic, CT-RFs) features which were correlated with clinico-pathological and TIME profiles to determine their impact on survival outcome. Results: Specific 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. Conclusion: Higher order CT extracted features associated with specific TIME profiles may reveal a radio-immune signature with prognostic impact on resected NSCLC.
Integrated CT imaging and tissue immune features disclose a radio-immune signature with high prognostic impact on surgically resected NSCLC / Mazzaschi, G.; Milanese, G.; Pagano, P.; Madeddu, D.; Gnetti, L.; Trentini, F.; Falco, A.; Frati, C.; Lorusso, B.; Lagrasta, C.; Minari, R.; Ampollini, L.; Silva, M.; Sverzellati, N.; Quaini, F.; Tiseo, M.; Roti, G.. - In: LUNG CANCER. - ISSN 0169-5002. - 144:(2020), pp. 30-39. [10.1016/j.lungcan.2020.04.006]
Integrated CT imaging and tissue immune features disclose a radio-immune signature with high prognostic impact on surgically resected NSCLC
Mazzaschi G.;Milanese G.;Pagano P.;Madeddu D.;Gnetti L.;Falco A.;Frati C.;Lorusso B.;Lagrasta C.;Ampollini L.;Silva M.;Sverzellati N.;Quaini F.;Tiseo M.;Roti G.
2020-01-01
Abstract
Objectives: 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. Materials and methods: 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-CD3high/PD-1-to-CD8low) or inert (CD8-to-CD3low/PD-1-to-CD8high) phenotypes. CT datasets acted as source for qualitative (semantic, CT-SFs) and quantitative (radiomic, CT-RFs) features which were correlated with clinico-pathological and TIME profiles to determine their impact on survival outcome. Results: Specific 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. Conclusion: Higher order CT extracted features associated with specific TIME profiles may reveal a radio-immune signature with prognostic impact on resected NSCLC.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
