Jiaqi Li1, Zhenbin Qiu2,3, Chao Zhang2,3, Sijie Chen1, Mengmin Wang2,3, Qiuchen Meng1, Haiming Lu1, Lei Wei1, Hairong Lv1,4, Wenzhao Zhong5,6, Xuegong Zhang7,8. 1. Bioinformatics Division, BNRIST and MOE Key Lab of Bioinformatics, Department of Automation, Tsinghua University, Beijing, China. 2. Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. 3. Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. 4. Fuzhou Institute of Data Technology, Fuzhou, China. 5. Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. sywenzhaozhong@scut.edu.cn. 6. Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. sywenzhaozhong@scut.edu.cn. 7. Bioinformatics Division, BNRIST and MOE Key Lab of Bioinformatics, Department of Automation, Tsinghua University, Beijing, China. zhangxg@tsinghua.edu.cn. 8. School of Medicine, Tsinghua University, Beijing, China. zhangxg@tsinghua.edu.cn.
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.
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.
Authors: K Kian Ang; Jonathan Harris; Richard Wheeler; Randal Weber; David I Rosenthal; Phuc Felix Nguyen-Tân; William H Westra; Christine H Chung; Richard C Jordan; Charles Lu; Harold Kim; Rita Axelrod; C Craig Silverman; Kevin P Redmond; Maura L Gillison Journal: N Engl J Med Date: 2010-06-07 Impact factor: 91.245
Authors: Brian O'Sullivan; Shao Hui Huang; Jie Su; Adam S Garden; Erich M Sturgis; Kristina Dahlstrom; Nancy Lee; Nadeem Riaz; Xin Pei; Shlomo A Koyfman; David Adelstein; Brian B Burkey; Jeppe Friborg; Claus A Kristensen; Anita B Gothelf; Frank Hoebers; Bernd Kremer; Ernst-Jan Speel; Daniel W Bowles; David Raben; Sana D Karam; Eugene Yu; Wei Xu Journal: Lancet Oncol Date: 2016-02-27 Impact factor: 41.316