Skip to main content
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 5/2020

14.11.2019 | Original Article

Value of pre-therapy 18F-FDG PET/CT radiomics in predicting EGFR mutation status in patients with non-small cell lung cancer

verfasst von: Jianyuan Zhang, Xinming Zhao, Yan Zhao, Jingmian Zhang, Zhaoqi Zhang, Jianfang Wang, Yingchen Wang, Meng Dai, Jingya Han

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 5/2020

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To assess the predictive power of pre-therapy 18F-FDG PET/CT-based radiomic features for epidermal growth factor receptor (EGFR) mutation status in non-small cell lung cancer.

Methods

Two hundred and forty-eight lung cancer patients underwent pre-therapy diagnostic 18F-FDG PET/CT scans and were tested for genetic mutations. The LIFEx package was used to extract 47 PET and 45 CT radiomic features reflecting tumor heterogeneity and phenotype. The least absolute shrinkage and selection operator (LASSO) algorithm was used to select radiomic features and develop a radiomics signature. We compared the predictive performance of models established by radiomics signature, clinical variables, and their combinations using receiver operating curves (ROCs). In addition, a nomogram based on the radiomics signature score (rad-score) and clinical variables was developed.

Results

The patients were divided into a training set (n = 175) and a validation set (n = 73). Ten radiomic features were selected to build the radiomics signature model. The model showed a significant ability to discriminate between EGFR mutation and EGFR wild type, with area under the ROC curve (AUC) equal to 0.79 in the training set, and 0.85 in the validation set, compared with 0.75 and 0.69 for the clinical model. When clinical variables and radiomics signature were combined, the AUC increased to 0.86 (95% CI [0.80–0.91]) in the training set and 0.87 (95% CI [0.79–0.95]) in the validation set, thus showing better performance in the prediction of EGFR mutations.

Conclusion

The PET/CT-based radiomic features showed good performance in predicting EGFR mutation in non-small cell lung cancer, providing a useful method for the choice of targeted therapy in a clinical setting.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Hsu WH, Yang JC, Mok TS, Loong HH. Overview of current systemic management of EGFR-mutant NSCLC. Ann Oncol. 2018;29:i3–9.CrossRef Hsu WH, Yang JC, Mok TS, Loong HH. Overview of current systemic management of EGFR-mutant NSCLC. Ann Oncol. 2018;29:i3–9.CrossRef
2.
Zurück zum Zitat An N, Zhang Y, Niu H, Li Z, Cai J, Zhao Q, et al. EGFR-TKIs versus taxanes agents in therapy for nonsmall-cell lung cancer patients: a PRISMA-compliant systematic review with meta-analysis and meta-regression. Medicine (Baltimore). 2016;95:e5601.CrossRef An N, Zhang Y, Niu H, Li Z, Cai J, Zhao Q, et al. EGFR-TKIs versus taxanes agents in therapy for nonsmall-cell lung cancer patients: a PRISMA-compliant systematic review with meta-analysis and meta-regression. Medicine (Baltimore). 2016;95:e5601.CrossRef
3.
Zurück zum Zitat Wang S, Shi J, Ye Z, Dong D, Yu D, Zhou M, et al. Predicting EGFR mutation status in lung adenocarcinoma on computed tomography image using deep learning. Eur Respir J. 2019;53:1800986.CrossRef Wang S, Shi J, Ye Z, Dong D, Yu D, Zhou M, et al. Predicting EGFR mutation status in lung adenocarcinoma on computed tomography image using deep learning. Eur Respir J. 2019;53:1800986.CrossRef
4.
Zurück zum Zitat Kuo MD, Jamshidi N. Behind the numbers: decoding molecular phenotypes with radiogenomics─guiding principles and technical considerations. Radiology. 2014;270(2):320–5.CrossRef Kuo MD, Jamshidi N. Behind the numbers: decoding molecular phenotypes with radiogenomics─guiding principles and technical considerations. Radiology. 2014;270(2):320–5.CrossRef
5.
Zurück zum Zitat Ozkan E, West A, Dedelow JA, Chu BF, Zhao W, Yildiz VO, et al. CT gray-level texture analysis as a quantitative imaging biomarker of epidermal growth factor receptor mutation status in adenocarcinoma of the lung. AJR Am J Roentgenol. 2015;205:1016–25.CrossRef Ozkan E, West A, Dedelow JA, Chu BF, Zhao W, Yildiz VO, et al. CT gray-level texture analysis as a quantitative imaging biomarker of epidermal growth factor receptor mutation status in adenocarcinoma of the lung. AJR Am J Roentgenol. 2015;205:1016–25.CrossRef
6.
Zurück zum Zitat Bianconi F, Fravolini ML, Bello-Cerezo R, Minestrini M, Scialpi M, Palumbo B. Evaluation of shape and textural features from CT as prognostic biomarkers in non-small cell lung cancer. Anticancer Res. 2018;38:2155–60.PubMed Bianconi F, Fravolini ML, Bello-Cerezo R, Minestrini M, Scialpi M, Palumbo B. Evaluation of shape and textural features from CT as prognostic biomarkers in non-small cell lung cancer. Anticancer Res. 2018;38:2155–60.PubMed
7.
Zurück zum Zitat Digumarthy SR, Padole AM, Gullo RL, Sequist LV, Kalra MK. Can CT radiomic analysis in NSCLC predict histology and EGFR mutation status? Medicine (Baltimore). 2019;98:e13963.CrossRef Digumarthy SR, Padole AM, Gullo RL, Sequist LV, Kalra MK. Can CT radiomic analysis in NSCLC predict histology and EGFR mutation status? Medicine (Baltimore). 2019;98:e13963.CrossRef
8.
Zurück zum Zitat Cook GJR, Azad G, Owczarczyk K, Siddique M, Goh V. Challenges and promises of PET radiomics. Int J Radiat Oncol Biol Phys. 2018;102:1083–9.CrossRef Cook GJR, Azad G, Owczarczyk K, Siddique M, Goh V. Challenges and promises of PET radiomics. Int J Radiat Oncol Biol Phys. 2018;102:1083–9.CrossRef
9.
Zurück zum Zitat Lee SM, Bae SK, Jung SJ, Kim CK. FDG uptake in non-small cell lung cancer is not an independent predictor of EGFR or KRAS mutation status: a retrospective analysis of 206 patients. Clin Nucl Med. 2015;40:950–8.CrossRef Lee SM, Bae SK, Jung SJ, Kim CK. FDG uptake in non-small cell lung cancer is not an independent predictor of EGFR or KRAS mutation status: a retrospective analysis of 206 patients. Clin Nucl Med. 2015;40:950–8.CrossRef
10.
Zurück zum Zitat Takamochi K, Mogushi K, Kawaji H, Imashimizu K, Fukui M, Oh S, et al. Correlation of EGFR or KRAS mutation status with 18F-FDG uptake on PET-CT scan in lung adenocarcinoma. PLoS One. 2017;12:e0175622.CrossRef Takamochi K, Mogushi K, Kawaji H, Imashimizu K, Fukui M, Oh S, et al. Correlation of EGFR or KRAS mutation status with 18F-FDG uptake on PET-CT scan in lung adenocarcinoma. PLoS One. 2017;12:e0175622.CrossRef
11.
Zurück zum Zitat Zwanenburg A, Leger S, Vallières M, Löck S, for the Image Biomarker Standardisation Initiative (IBSI). Image biomarker standardisation initiative — feature definitions. 2018 [Current version V10 2019]. https://arxiv.org/abs/1612.07003. Zwanenburg A, Leger S, Vallières M, Löck S, for the Image Biomarker Standardisation Initiative (IBSI). Image biomarker standardisation initiative — feature definitions. 2018 [Current version V10 2019]. https://​arxiv.​org/​abs/​1612.​07003.
12.
Zurück zum Zitat Boellaard R, Delgado-Bolton R, Oyen WJ, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015;42:328–54.CrossRef Boellaard R, Delgado-Bolton R, Oyen WJ, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015;42:328–54.CrossRef
13.
Zurück zum Zitat Nioche C, Orlhac F, Boughdad S, Reuzé S, Goya-Outi J, Robert C, et al. LIFEx: a freeware for radiomic feature calculation in multimodality imaging to accelerate advances in the characterization of tumor heterogeneity. Cancer Res. 2018;78:4786–9.CrossRef Nioche C, Orlhac F, Boughdad S, Reuzé S, Goya-Outi J, Robert C, et al. LIFEx: a freeware for radiomic feature calculation in multimodality imaging to accelerate advances in the characterization of tumor heterogeneity. Cancer Res. 2018;78:4786–9.CrossRef
14.
Zurück zum Zitat Kirienko M, Cozzi L, Rossi A, Voulaz E, Antunovic L, Fogliata A, et al. Ability of FDG PET and CT radiomics features to differentiate between primary and metastatic lung lesions. Eur J Nucl Med Mol Imaging. 2018;45:1649–60.CrossRef Kirienko M, Cozzi L, Rossi A, Voulaz E, Antunovic L, Fogliata A, et al. Ability of FDG PET and CT radiomics features to differentiate between primary and metastatic lung lesions. Eur J Nucl Med Mol Imaging. 2018;45:1649–60.CrossRef
15.
Zurück zum Zitat She Y, Zhang L, Zhu H, Dai C, Xie D, Xie H, et al. The predictive value of CT-based radiomics in differentiating indolent from invasive lung adenocarcinoma in patients with pulmonary nodules. Eur Radiol. 2018;28:5121–8.CrossRef She Y, Zhang L, Zhu H, Dai C, Xie D, Xie H, et al. The predictive value of CT-based radiomics in differentiating indolent from invasive lung adenocarcinoma in patients with pulmonary nodules. Eur Radiol. 2018;28:5121–8.CrossRef
16.
Zurück zum Zitat Goldman JW, Noor ZS, Remon J, Besse B, Rosenfeld N. Are liquid biopsies a surrogate for tissue EGFR testing? Ann Oncol. 2018;29:i38–46.CrossRef Goldman JW, Noor ZS, Remon J, Besse B, Rosenfeld N. Are liquid biopsies a surrogate for tissue EGFR testing? Ann Oncol. 2018;29:i38–46.CrossRef
17.
Zurück zum Zitat Kim TO, Oh IJ, Kho BG, Park HY, Chang JS, Park CK, et al. Feasibility of re-biopsy and EGFR mutation analysis in patients with non-small cell lung cancer. Thorac Cancer. 2018;9:856–64.CrossRef Kim TO, Oh IJ, Kho BG, Park HY, Chang JS, Park CK, et al. Feasibility of re-biopsy and EGFR mutation analysis in patients with non-small cell lung cancer. Thorac Cancer. 2018;9:856–64.CrossRef
18.
Zurück zum Zitat Li W, Qiu T, Ling Y, Gao S, Ying J. Subjecting appropriate lung adenocarcinoma samples to next-generation sequencing-based molecular testing: challenges and possible solutions. Mol Oncol. 2018;12:677–89.CrossRef Li W, Qiu T, Ling Y, Gao S, Ying J. Subjecting appropriate lung adenocarcinoma samples to next-generation sequencing-based molecular testing: challenges and possible solutions. Mol Oncol. 2018;12:677–89.CrossRef
19.
Zurück zum Zitat Kim YI, Paeng JC, Park YS, Cheon GJ, Lee DS, Chung JK, et al. Relation of EGFR mutation status to metabolic activity in localized lung adenocarcinoma and its influence on the use of FDG PET/CT parameters in prognosis. AJR Am J Roentgenol. 2018;210:1346–51.CrossRef Kim YI, Paeng JC, Park YS, Cheon GJ, Lee DS, Chung JK, et al. Relation of EGFR mutation status to metabolic activity in localized lung adenocarcinoma and its influence on the use of FDG PET/CT parameters in prognosis. AJR Am J Roentgenol. 2018;210:1346–51.CrossRef
20.
Zurück zum Zitat Weihua Z, Tsan R, Huang WC, Wu Q, Chiu CH, Fidler IJ, et al. Survival of cancer cells is maintained by EGFR independent of its kinase activity. Cancer Cell. 2008;13:385–93.CrossRef Weihua Z, Tsan R, Huang WC, Wu Q, Chiu CH, Fidler IJ, et al. Survival of cancer cells is maintained by EGFR independent of its kinase activity. Cancer Cell. 2008;13:385–93.CrossRef
21.
Zurück zum Zitat Rizzo S, Petrella F, Buscarino V, De Maria F, Raimondi S, Barberis M, et al. CT radiogenomic characterization of EGFR, K-RAS, and ALK mutations in non-small cell lung cancer. Eur Radiol. 2016;26:32–42.CrossRef Rizzo S, Petrella F, Buscarino V, De Maria F, Raimondi S, Barberis M, et al. CT radiogenomic characterization of EGFR, K-RAS, and ALK mutations in non-small cell lung cancer. Eur Radiol. 2016;26:32–42.CrossRef
22.
Zurück zum Zitat Liu Y, Kim J, Qu F, Liu S, Wang H, Balagurunathan Y, et al. CT features associated with epidermal growth factor receptor mutation status in patients with lung adenocarcinoma. Radiology. 2016;280:271–80.CrossRef Liu Y, Kim J, Qu F, Liu S, Wang H, Balagurunathan Y, et al. CT features associated with epidermal growth factor receptor mutation status in patients with lung adenocarcinoma. Radiology. 2016;280:271–80.CrossRef
23.
Zurück zum Zitat Shi Z, Zheng X, Shi R, Song C, Yang R, Zhang Q, et al. Radiological and clinical features associated with epidermal growth factor receptor mutation status of Exon 19 and 21 in lung adenocarcinoma. Sci Rep. 2017;7:364.CrossRef Shi Z, Zheng X, Shi R, Song C, Yang R, Zhang Q, et al. Radiological and clinical features associated with epidermal growth factor receptor mutation status of Exon 19 and 21 in lung adenocarcinoma. Sci Rep. 2017;7:364.CrossRef
24.
Zurück zum Zitat Sacconi B, Anzidei M, Leonardi A, Boni F, Saba L, Scipione R, et al. Analysis of CT features and quantitative texture analysis in patients with lung adenocarcinoma: a correlation with EGFR mutations and survival rates. Clin Radiol. 2017;72:443–50.CrossRef Sacconi B, Anzidei M, Leonardi A, Boni F, Saba L, Scipione R, et al. Analysis of CT features and quantitative texture analysis in patients with lung adenocarcinoma: a correlation with EGFR mutations and survival rates. Clin Radiol. 2017;72:443–50.CrossRef
25.
Zurück zum Zitat Desseroit MC. Tixier F, Weber WA, Siegel BA, Cheze Le Rest C, Visvikis D, et al. Reliability of PET/CT shape and heterogeneity features in functional and morphologic components of non-small cell lung cancer tumors: a repeatability analysis in a prospective multicenter cohort. J Nucl Med. 2017;58:406–11.CrossRef Desseroit MC. Tixier F, Weber WA, Siegel BA, Cheze Le Rest C, Visvikis D, et al. Reliability of PET/CT shape and heterogeneity features in functional and morphologic components of non-small cell lung cancer tumors: a repeatability analysis in a prospective multicenter cohort. J Nucl Med. 2017;58:406–11.CrossRef
26.
Zurück zum Zitat Aerts HJ, Velazquez ER, Leijenaar RT, Parmar C, Grossmann P, Carvalho S, et al. Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach. Nat Commun. 2014;5:4006.CrossRef Aerts HJ, Velazquez ER, Leijenaar RT, Parmar C, Grossmann P, Carvalho S, et al. Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach. Nat Commun. 2014;5:4006.CrossRef
27.
Zurück zum Zitat Yip SS, Kim J, Coroller TP, Parmar C, Velazquez ER, Huynh E, et al. Associations between somatic mutations and metabolic imaging phenotypes in non-small cell lung cancer. J Nucl Med. 2017;58:569–76.CrossRef Yip SS, Kim J, Coroller TP, Parmar C, Velazquez ER, Huynh E, et al. Associations between somatic mutations and metabolic imaging phenotypes in non-small cell lung cancer. J Nucl Med. 2017;58:569–76.CrossRef
28.
Zurück zum Zitat Rios Velazquez E, Parmar C, Liu Y, Coroller TP, Cruz G, Stringfield O, et al. Somatic mutations drive distinct imaging phenotypes in lung cancer. Cancer Res. 2017;77:3922–30.CrossRef Rios Velazquez E, Parmar C, Liu Y, Coroller TP, Cruz G, Stringfield O, et al. Somatic mutations drive distinct imaging phenotypes in lung cancer. Cancer Res. 2017;77:3922–30.CrossRef
29.
Zurück zum Zitat Dogan S, Shen R, Ang DC, Johnson ML, D’Angelo SP, Paik PK, et al. Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: higher susceptibility of women to smoking-related KRAS-mutant cancers. Clin Cancer Res. 2012;18:6169–77.CrossRef Dogan S, Shen R, Ang DC, Johnson ML, D’Angelo SP, Paik PK, et al. Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: higher susceptibility of women to smoking-related KRAS-mutant cancers. Clin Cancer Res. 2012;18:6169–77.CrossRef
30.
Zurück zum Zitat Shi Y, Au JS, Thongprasert S, Srinivasan S, Tsai CM, Khoa MT, et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol. 2014;9:154–62.CrossRef Shi Y, Au JS, Thongprasert S, Srinivasan S, Tsai CM, Khoa MT, et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol. 2014;9:154–62.CrossRef
31.
Zurück zum Zitat Liu Y, Kim J, Balagurunathan Y, Li Q, Garcia AL, Stringfield O, et al. Radiomic features are associated with EGFR mutation status in lung adenocarcinomas. Clin Lung Cancer. 2016;17:441–8.e6.CrossRef Liu Y, Kim J, Balagurunathan Y, Li Q, Garcia AL, Stringfield O, et al. Radiomic features are associated with EGFR mutation status in lung adenocarcinomas. Clin Lung Cancer. 2016;17:441–8.e6.CrossRef
32.
Zurück zum Zitat Zhang L, Chen B, Liu X, Song J, Fang M, Hu C, et al. Quantitative biomarkers for prediction of epidermal growth factor receptor mutation in non-small cell lung cancer. Transl Oncol. 2018;11:94–101.CrossRef Zhang L, Chen B, Liu X, Song J, Fang M, Hu C, et al. Quantitative biomarkers for prediction of epidermal growth factor receptor mutation in non-small cell lung cancer. Transl Oncol. 2018;11:94–101.CrossRef
Metadaten
Titel
Value of pre-therapy 18F-FDG PET/CT radiomics in predicting EGFR mutation status in patients with non-small cell lung cancer
verfasst von
Jianyuan Zhang
Xinming Zhao
Yan Zhao
Jingmian Zhang
Zhaoqi Zhang
Jianfang Wang
Yingchen Wang
Meng Dai
Jingya Han
Publikationsdatum
14.11.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 5/2020
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-019-04592-1

Weitere Artikel der Ausgabe 5/2020

European Journal of Nuclear Medicine and Molecular Imaging 5/2020 Zur Ausgabe