ITHscore: comprehensive quantification of intra-tumor heterogeneity in NSCLC by multi-scale radiomic features.

ABSTRACT

OBJECTIVES: To quantify intra-tumor heterogeneity (ITH) in non-small cell lung cancer (NSCLC) from computed tomography (CT) images. METHODS: We developed a quantitative ITH measurement-ITHscore-by integrating local radiomic features and global pixel distribution patterns. The associations of ITHscore with tumor phenotypes, genotypes, and patient's prognosis were examined on six patient cohorts (n = 1399) to validate its effectiveness in characterizing ITH. RESULTS: For stage I NSCLC, ITHscore was consistent with tumor progression from stage IA1 to IA3 (p < 0.001) and captured key pathological change in terms of malignancy (p < 0.001). ITHscore distinguished the presence of lymphovascular invasion (p = 0.003) and pleural invasion (p = 0.001) in tumors. ITHscore also separated patient groups with different overall survival (p = 0.004) and disease-free survival conditions (p = 0.005). Radiogenomic analysis showed that the level of ITHscore in stage I and stage II NSCLC is correlated with heterogeneity-related pathways. In addition, ITHscore was proved to be a stable measurement and can be applied to ITH quantification in head-and-neck cancer (HNC). CONCLUSIONS: ITH in NSCLC can be quantified from CT images by ITHscore, which is an indicator for tumor phenotypes and patient's prognosis. KEY POINTS • ITHscore provides a radiomic quantification of intra-tumor heterogeneity in NSCLC. • ITHscore is an indicator for tumor phenotypes and patient's prognosis. • ITHscore has the potential to be generalized to other cancer types such as HNC.