Prognostic analysis and risk stratification of lung adenocarcinoma undergoing EGFR-TKI therapy with time-serial CT-based radiomics signature

OBJECTIVES: To evaluate the value of time-serial CT radiomics features in predicting progression-free survival (PFS) for lung adenocarcinoma (LUAD) patients after epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) therapy. MATERIALS AND METHODS: LUAD patients treated with EGFR-TKIs were retrospectively included from three independent institutes and divided into training and validation cohorts. Intratumoral and peritumoral features were extracted from time-serial non-contrast chest CT (including pre-therapy and first follow-up images); moreover, the percentage variation per unit time (day) was introduced to adjust for the different follow-up periods of each patient. Test-retest was performed to exclude irreproducible features, while the Boruta algorithm was used to select critical radiomics features. Radiomics signatures were constructed with random forest survival models in the training cohort and compared against baseline clinical characteristics through Cox regression and nonparametric testing of concordance indices (C-indices). RESULTS: The training cohort included 131 patients (74 women, 56.5%) from one institute and the validation cohort encompassed 41 patients (24 women, 58.5%) from two other institutes. The optimal signature contained 10 features and 7 were unit time feature variations. The comprehensive radiomics model outperformed the pre-therapy clinical characteristics in predicting PFS (training: 0.78, 95% CI: [0.72, 0.84] versus 0.55, 95% CI: [0.49, 0.62], p < 0.001; validation: 0.72, 95% CI: [0.60, 0.84] versus 0.54, 95% CI: [0.42, 0.66], p < 0.001). CONCLUSION: Radiomics signature derived from time-serial CT images demonstrated optimal prognostic performance of disease progression. This dynamic imaging biomarker holds the promise of monitoring treatment response and achieving personalized management. KEY POINTS: • The intrinsic tumor heterogeneity can be highly dynamic under the therapeutic effect of EGFR-TKI treatment, and the inevitable development of drug resistance may disrupt the duration of clinical benefit. Decision-making remained challenging in practice to detect the emergence of acquired resistance during the early response phase. • Time-serial CT-based radiomics signature integrating intra- and peritumoral features offered the potential to predict progression-free survival for LUAD patients treated with EGFR-TKIs. • The dynamic imaging signature allowed for prognostic risk stratification. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00330-022-09123-5.