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Published in: European Journal of Nuclear Medicine and Molecular Imaging 2/2021

01-02-2021 | Lymphoma | Original Article

The deep learning model combining CT image and clinicopathological information for predicting ALK fusion status and response to ALK-TKI therapy in non-small cell lung cancer patients

Authors: Zhengbo Song, Tianchi Liu, Lei Shi, Zongyang Yu, Qing Shen, Mengdi Xu, Zhangzhou Huang, Zhijian Cai, Wenxian Wang, Chunwei Xu, Jingjing Sun, Ming Chen

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 2/2021

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Abstract

Purpose

This study aimed to investigate the deep learning model (DLM) combining computed tomography (CT) images and clinicopathological information for predicting anaplastic lymphoma kinase (ALK) fusion status in non-small cell lung cancer (NSCLC) patients.

Materials and methods

Preoperative CT images, clinicopathological information as well as the ALK fusion status from 937 patients in three hospitals were retrospectively collected to train and validate the DLM for the prediction of ALK fusion status in tumors. Another cohort of patients (n = 91) received ALK tyrosine kinase inhibitor (TKI) treatment was also included to evaluate the value of the DLM in predicting the clinical outcomes of the patients.

Results

The performances of the DLM trained only by CT images in the primary and validation cohorts were AUC = 0.8046 (95% CI 0.7715–0.8378) and AUC = 0.7754 (95% CI 0.7199–0.8310), respectively, while the DLM trained by both CT images and clinicopathological information exhibited better performance for the prediction of ALK fusion status (AUC = 0.8540, 95% CI 0.8257–0.8823 in the primary cohort, p < 0.001; AUC = 0.8481, 95% CI 0.8036–0.8926 in the validation cohort, p < 0.001). In addition, the deep learning scores of the DLMs showed significant differences between the wild-type and ALK infusion tumors. In the ALK-target therapy cohort (n = 91), the patients predicted as ALK-positive by the DLM showed better performance of progression-free survival than the patients predicted as ALK-negative (16.8 vs. 7.5 months, p = 0.010).

Conclusion

Our findings showed that the DLM trained by both CT images and clinicopathological information could effectively predict the ALK fusion status and treatment responses of patients. For the small size of the ALK-target therapy cohort, larger data sets would be collected to further validate the performance of the model for predicting the response to ALK-TKI treatment.
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Literature
2.
go back to reference Blackhall FH, Peters S, Bubendorf L, et al. Prevalence and clinical outcomes for patients with ALK-positive resected stage I to III adenocarcinoma: results from the European Thoracic Oncology Platform Lungscape project. J Clin Oncol. American Society of Clinical Oncology. 2014;32(25):2780–7.CrossRef Blackhall FH, Peters S, Bubendorf L, et al. Prevalence and clinical outcomes for patients with ALK-positive resected stage I to III adenocarcinoma: results from the European Thoracic Oncology Platform Lungscape project. J Clin Oncol. American Society of Clinical Oncology. 2014;32(25):2780–7.CrossRef
5.
go back to reference Solomon BJ, Kim DW, Wu YL, et al. Final overall survival analysis from a study comparing first-line crizotinib versus chemotherapy in alk-mutation-positive non–small-cell lung cancer. J Clin Oncol. American Society of Clinical Oncology. 2018;36(22):2251–8.CrossRef Solomon BJ, Kim DW, Wu YL, et al. Final overall survival analysis from a study comparing first-line crizotinib versus chemotherapy in alk-mutation-positive non–small-cell lung cancer. J Clin Oncol. American Society of Clinical Oncology. 2018;36(22):2251–8.CrossRef
7.
go back to reference Ou SHI, Ahn JS, De Petris L, et al. Alectinib in crizotinib-refractory alk-rearranged non-small-cell lung cancer: a phase II global study. J Clin Oncol. American Society of Clinical Oncology. 2016;34(7):661–8.CrossRef Ou SHI, Ahn JS, De Petris L, et al. Alectinib in crizotinib-refractory alk-rearranged non-small-cell lung cancer: a phase II global study. J Clin Oncol. American Society of Clinical Oncology. 2016;34(7):661–8.CrossRef
8.
go back to reference Shaw AT, Solomon BJ, Besse B, et al. ALK resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non–small-cell lung cancer. J Clin Oncol. American Society of Clinical Oncology; 2019;37(16):1370–1379. https://pubmed.ncbi.nlm.nih.gov/30892989/. Accessed 10 July 2020. Shaw AT, Solomon BJ, Besse B, et al. ALK resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non–small-cell lung cancer. J Clin Oncol. American Society of Clinical Oncology; 2019;37(16):1370–1379. https://​pubmed.​ncbi.​nlm.​nih.​gov/​30892989/​. Accessed 10 July 2020.
9.
10.
go back to reference McLeer-Florin A, Duruisseaux M, Pinsolle J, et al. ALK fusion variants detection by targeted RNA-next generation sequencing and clinical responses to crizotinib in ALK-positive non-small cell lung cancer. Lung Cancer Elsevier Ireland Ltd. 2018;116:15–24.CrossRef McLeer-Florin A, Duruisseaux M, Pinsolle J, et al. ALK fusion variants detection by targeted RNA-next generation sequencing and clinical responses to crizotinib in ALK-positive non-small cell lung cancer. Lung Cancer Elsevier Ireland Ltd. 2018;116:15–24.CrossRef
12.
go back to reference McCoach CE, Blakely CM, Banks KC, et al. Clinical utility of cell-free DNA for the detection of ALK fusions and genomic mechanisms of ALK inhibitor resistance in non-small cell lung cancer. Clin Cancer Res NIH Public Access. 2018;24(12):2758.CrossRef McCoach CE, Blakely CM, Banks KC, et al. Clinical utility of cell-free DNA for the detection of ALK fusions and genomic mechanisms of ALK inhibitor resistance in non-small cell lung cancer. Clin Cancer Res NIH Public Access. 2018;24(12):2758.CrossRef
13.
go back to reference Gevaert O, Echegaray S, Khuong A, et al. Predictive radiogenomics modeling of EGFR mutation status in lung cancer. Sci Rep Nature Publishing Group. 2017;7(1):1–8.CrossRef Gevaert O, Echegaray S, Khuong A, et al. Predictive radiogenomics modeling of EGFR mutation status in lung cancer. Sci Rep Nature Publishing Group. 2017;7(1):1–8.CrossRef
14.
go back to reference Yip SSF, Kim J, Coroller TP, et al. Associations between somatic mutations and metabolic imaging phenotypes in non-small cell lung cancer. J Nucl Med. Society of Nuclear Medicine Inc. 2017;58(4):569–76.CrossRef Yip SSF, Kim J, Coroller TP, et al. Associations between somatic mutations and metabolic imaging phenotypes in non-small cell lung cancer. J Nucl Med. Society of Nuclear Medicine Inc. 2017;58(4):569–76.CrossRef
15.
go back to reference Yoon HJ, Sohn I, Cho JH, et al. Decoding tumor phenotypes for ALK, ROS1, and RET fusions in lung adenocarcinoma using a radiomics approach. Med (United States). 2015;94(41):1–8. Yoon HJ, Sohn I, Cho JH, et al. Decoding tumor phenotypes for ALK, ROS1, and RET fusions in lung adenocarcinoma using a radiomics approach. Med (United States). 2015;94(41):1–8.
16.
go back to reference Radiol CJ. Preliminary value of CT radiomics in predicting anaplastic lymphoma kinase fusion gene expression in lung adenocarcinoma. Chin J Radiol. 2015;49(2):89–94. Radiol CJ. Preliminary value of CT radiomics in predicting anaplastic lymphoma kinase fusion gene expression in lung adenocarcinoma. Chin J Radiol. 2015;49(2):89–94.
17.
go back to reference Grove O, Berglund AE, Schabath MB, et al. Quantitative computed tomographic descriptors associate tumor shape complexity and intratumor heterogeneity with prognosis in lung adenocarcinoma. Muñoz-Barrutia A, editor. PLoS One. Public Library of Science; 2015;10(3):e0118261. https://doi.org/10.1371/journal.pone.0118261. Accessed 10 Mar 2020. Grove O, Berglund AE, Schabath MB, et al. Quantitative computed tomographic descriptors associate tumor shape complexity and intratumor heterogeneity with prognosis in lung adenocarcinoma. Muñoz-Barrutia A, editor. PLoS One. Public Library of Science; 2015;10(3):e0118261. https://​doi.​org/​10.​1371/​journal.​pone.​0118261. Accessed 10 Mar 2020.
18.
go back to reference Fried DV, Tucker SL, Zhou S, et al. Prognostic value and reproducibility of pretreatment ct texture features in stage III non-small cell lung cancer. Int J Radiat Oncol Biol Phys. Elsevier Inc. 2014;90(4):834–42.CrossRef Fried DV, Tucker SL, Zhou S, et al. Prognostic value and reproducibility of pretreatment ct texture features in stage III non-small cell lung cancer. Int J Radiat Oncol Biol Phys. Elsevier Inc. 2014;90(4):834–42.CrossRef
19.
go back to reference Song J, Shi J, Dong D, et al. A new approach to predict progression-free survival in stage IV EGFR-mutant NSCLC patients with EGFR-TKI therapy. Clin Cancer Res. American Association for Cancer Research Inc.; 2018;24(15):3583–3592. https://pubmed.ncbi.nlm.nih.gov/29563137/. Accessed 10 July 2020. Song J, Shi J, Dong D, et al. A new approach to predict progression-free survival in stage IV EGFR-mutant NSCLC patients with EGFR-TKI therapy. Clin Cancer Res. American Association for Cancer Research Inc.; 2018;24(15):3583–3592. https://​pubmed.​ncbi.​nlm.​nih.​gov/​29563137/​. Accessed 10 July 2020.
20.
go back to reference Yang X, Dong X, Wang J, et al. Computed tomography-based radiomics signature: a potential indicator of epidermal growth factor receptor mutation in pulmonary adenocarcinoma appearing as a subsolid nodule. Oncologist. 2019;24(11):1156–64.CrossRef Yang X, Dong X, Wang J, et al. Computed tomography-based radiomics signature: a potential indicator of epidermal growth factor receptor mutation in pulmonary adenocarcinoma appearing as a subsolid nodule. Oncologist. 2019;24(11):1156–64.CrossRef
21.
go back to reference Velazquez ER, Parmar C, Liu Y, et al. Somatic mutations drive distinct imaging phenotypes in lung cancer 2018;77(14):3922–3930. Velazquez ER, Parmar C, Liu Y, et al. Somatic mutations drive distinct imaging phenotypes in lung cancer 2018;77(14):3922–3930.
22.
go back to reference Tang C, Hobbs B, Amer A, et al. Development of an immune-pathology informed radiomics model for non-small cell lung cancer. Sci Rep Springer US. 2018;8(1):1–9.CrossRef Tang C, Hobbs B, Amer A, et al. Development of an immune-pathology informed radiomics model for non-small cell lung cancer. Sci Rep Springer US. 2018;8(1):1–9.CrossRef
23.
go back to reference Yoon J, Suh YJ, Han K, et al. Utility of CT radiomics for prediction of PD-L1 expression in advanced lung adenocarcinomas. Thorac Cancer. 2020:1–12. Yoon J, Suh YJ, Han K, et al. Utility of CT radiomics for prediction of PD-L1 expression in advanced lung adenocarcinomas. Thorac Cancer. 2020:1–12.
24.
go back to reference Gulshan V, Peng L, Coram M, et al. Development and validation of a deep learning algorithm for detection of diabetic retinopathy in retinal fundus photographs. JAMA J Am Med Assoc. 2016;316(22):2402–10.CrossRef Gulshan V, Peng L, Coram M, et al. Development and validation of a deep learning algorithm for detection of diabetic retinopathy in retinal fundus photographs. JAMA J Am Med Assoc. 2016;316(22):2402–10.CrossRef
27.
go back to reference Wang S, Shi J, Ye Z, et al. Predicting EGFR mutation status in lung adenocarcinoma on computed tomography image using deep learning. Eur Respir J. 2019;53(3). Wang S, Shi J, Ye Z, et al. Predicting EGFR mutation status in lung adenocarcinoma on computed tomography image using deep learning. Eur Respir J. 2019;53(3).
28.
go back to reference Zhao W, Yang J, Ni B, et al. Toward automatic prediction of EGFR mutation status in pulmonary adenocarcinoma with 3D deep learning. Cancer Med Blackwell Publishing Ltd. 2019;8(7):3532–43.CrossRef Zhao W, Yang J, Ni B, et al. Toward automatic prediction of EGFR mutation status in pulmonary adenocarcinoma with 3D deep learning. Cancer Med Blackwell Publishing Ltd. 2019;8(7):3532–43.CrossRef
29.
go back to reference He K, Zhang X, Ren S, Sun J. Identity mappings in deep residual networks. Lect Notes Comput Sci (including Subser Lect Notes Artif Intell Lect Notes Bioinformatics). Springer Verlag; 2016;9908 LNCS:630–645. http://arxiv.org/abs/1603.05027. Accessed 10 Apr 2020. He K, Zhang X, Ren S, Sun J. Identity mappings in deep residual networks. Lect Notes Comput Sci (including Subser Lect Notes Artif Intell Lect Notes Bioinformatics). Springer Verlag; 2016;9908 LNCS:630–645. http://​arxiv.​org/​abs/​1603.​05027. Accessed 10 Apr 2020.
30.
go back to reference He K, Zhang X, Ren S, Sun J. Deep residual learning for image recognition. Proc IEEE Comput Soc Conf Comput Vis Pattern Recognit. IEEE Computer Society; 2016. p. 770–778. He K, Zhang X, Ren S, Sun J. Deep residual learning for image recognition. Proc IEEE Comput Soc Conf Comput Vis Pattern Recognit. IEEE Computer Society; 2016. p. 770–778.
31.
go back to reference Ioffe S, Szegedy C. Batch normalization: accelerating deep network training by reducing internal covariate shift. 32nd Int. Conf. Mach. Learn. ICML 2015. 2015. Ioffe S, Szegedy C. Batch normalization: accelerating deep network training by reducing internal covariate shift. 32nd Int. Conf. Mach. Learn. ICML 2015. 2015.
32.
go back to reference Srivastava N, Hinton G, Krizhevsky A, Salakhutdinov R. Dropout: a simple way to prevent neural networks from overfitting. J. Mach. Learn. Res. 2014. Srivastava N, Hinton G, Krizhevsky A, Salakhutdinov R. Dropout: a simple way to prevent neural networks from overfitting. J. Mach. Learn. Res. 2014.
33.
go back to reference Nesterov Y. Gradient methods for minimizing composite functions. Math Program, Ser B. 2013;140:125–61.CrossRef Nesterov Y. Gradient methods for minimizing composite functions. Math Program, Ser B. 2013;140:125–61.CrossRef
34.
go back to reference He K, Zhang X, Ren S, Sun J. Delving deep into rectifiers: surpassing human-level performance on imagenet classification. Proc IEEE Int Conf Comput Vis. 2015;2015 Inter:1026–34. He K, Zhang X, Ren S, Sun J. Delving deep into rectifiers: surpassing human-level performance on imagenet classification. Proc IEEE Int Conf Comput Vis. 2015;2015 Inter:1026–34.
35.
go back to reference Conklin CMJ, Craddock KJ, Have C, Laskin J, Couture C, Ionescu DN. Immunohistochemistry is a reliable screening tool for identification of ALK rearrangement in non-small-cell lung carcinoma and is antibody dependent. J Thorac Oncol. Lippincott Williams and Wilkins. 2013;8(1):45–51.CrossRef Conklin CMJ, Craddock KJ, Have C, Laskin J, Couture C, Ionescu DN. Immunohistochemistry is a reliable screening tool for identification of ALK rearrangement in non-small-cell lung carcinoma and is antibody dependent. J Thorac Oncol. Lippincott Williams and Wilkins. 2013;8(1):45–51.CrossRef
37.
go back to reference Huang YQ, Liang CH, He L, et al. Development and validation of a radiomics nomogram for preoperative prediction of lymph node metastasis in colorectal cancer. J Clin Oncol. 2016;34(18):2157–64.CrossRef Huang YQ, Liang CH, He L, et al. Development and validation of a radiomics nomogram for preoperative prediction of lymph node metastasis in colorectal cancer. J Clin Oncol. 2016;34(18):2157–64.CrossRef
38.
go back to reference Selvaraju RR, Cogswell M, Das A, Vedantam R, Parikh D, Batra D. Grad-CAM: visual explanations from deep networks via gradient-based localization. Proc IEEE Int Conf Comput Vis. Institute of Electrical and Electronics Engineers Inc.; 2017. p. 618–626. Selvaraju RR, Cogswell M, Das A, Vedantam R, Parikh D, Batra D. Grad-CAM: visual explanations from deep networks via gradient-based localization. Proc IEEE Int Conf Comput Vis. Institute of Electrical and Electronics Engineers Inc.; 2017. p. 618–626.
39.
go back to reference Zhou Q, Zhang X-C, Chen Z-H, et al. Relative abundance of EGFR mutations predicts benefit from gefitinib treatment for advanced non-small-cell lung cancer. J Clin Oncol. American Society of Clinical Oncology; 2011;29(24):3316–3321. http://www.ncbi.nlm.nih.gov/pubmed/21788562. Accessed July 11, 2020. Zhou Q, Zhang X-C, Chen Z-H, et al. Relative abundance of EGFR mutations predicts benefit from gefitinib treatment for advanced non-small-cell lung cancer. J Clin Oncol. American Society of Clinical Oncology; 2011;29(24):3316–3321. http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​21788562. Accessed July 11, 2020.
Metadata
Title
The deep learning model combining CT image and clinicopathological information for predicting ALK fusion status and response to ALK-TKI therapy in non-small cell lung cancer patients
Authors
Zhengbo Song
Tianchi Liu
Lei Shi
Zongyang Yu
Qing Shen
Mengdi Xu
Zhangzhou Huang
Zhijian Cai
Wenxian Wang
Chunwei Xu
Jingjing Sun
Ming Chen
Publication date
01-02-2021
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 2/2021
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-020-04986-6

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