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Published in: European Journal of Nuclear Medicine and Molecular Imaging 10/2021

Open Access 01-09-2021 | Lung Cancer | Original Article

Just another “Clever Hans”? Neural networks and FDG PET-CT to predict the outcome of patients with breast cancer

Authors: Manuel Weber, David Kersting, Lale Umutlu, Michael Schäfers, Christoph Rischpler, Wolfgang P. Fendler, Irène Buvat, Ken Herrmann, Robert Seifert

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 10/2021

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Abstract

Background

Manual quantification of the metabolic tumor volume (MTV) from whole-body 18F-FDG PET/CT is time consuming and therefore usually not applied in clinical routine. It has been shown that neural networks might assist nuclear medicine physicians in such quantification tasks. However, little is known if such neural networks have to be designed for a specific type of cancer or whether they can be applied to various cancers. Therefore, the aim of this study was to evaluate the accuracy of a neural network in a cancer that was not used for its training.

Methods

Fifty consecutive breast cancer patients that underwent 18F-FDG PET/CT were included in this retrospective analysis. The PET-Assisted Reporting System (PARS) prototype that uses a neural network trained on lymphoma and lung cancer 18F-FDG PET/CT data had to detect pathological foci and determine their anatomical location. Consensus reads of two nuclear medicine physicians together with follow-up data served as diagnostic reference standard; 1072 18F-FDG avid foci were manually segmented. The accuracy of the neural network was evaluated with regard to lesion detection, anatomical position determination, and total tumor volume quantification.

Results

If PERCIST measurable foci were regarded, the neural network displayed high per patient sensitivity and specificity in detecting suspicious 18F-FDG foci (92%; CI = 79–97% and 98%; CI = 94–99%). If all FDG-avid foci were regarded, the sensitivity degraded (39%; CI = 30–50%). The localization accuracy was high for body part (98%; CI = 95–99%), region (88%; CI = 84–90%), and subregion (79%; CI = 74–84%). There was a high correlation of AI derived and manually segmented MTV (R2 = 0.91; p < 0.001). AI-derived whole-body MTV (HR = 1.275; CI = 1.208–1.713; p < 0.001) was a significant prognosticator for overall survival. AI-derived lymph node MTV (HR = 1.190; CI = 1.022–1.384; p = 0.025) and liver MTV (HR = 1.149; CI = 1.001–1.318; p = 0.048) were predictive for overall survival in a multivariate analysis.

Conclusion

Although trained on lymphoma and lung cancer, PARS showed good accuracy in the detection of PERCIST measurable lesions. Therefore, the neural network seems not prone to the clever Hans effect. However, the network has poor accuracy if all manually segmented lesions were used as reference standard. Both the whole body and organ-wise MTV were significant prognosticators of overall survival in advanced breast cancer.
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Literature
1.
go back to reference Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32:3059–67.CrossRef Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32:3059–67.CrossRef
2.
go back to reference Sheikhbahaei S, Mena E, Yanamadala A, et al. The value of FDG PET/CT in treatment response assessment, follow-up, and surveillance of lung cancer. Am J Roentgenol. 2017;208:420–33.CrossRef Sheikhbahaei S, Mena E, Yanamadala A, et al. The value of FDG PET/CT in treatment response assessment, follow-up, and surveillance of lung cancer. Am J Roentgenol. 2017;208:420–33.CrossRef
3.
go back to reference Groheux D, Cochet A, Humbert O, Alberini JL, Hindié E, Mankoff D. 18F-FDG PET/CT for staging and restaging of breast cancer. J Nucl Med. 2016;57:17S–26S.CrossRef Groheux D, Cochet A, Humbert O, Alberini JL, Hindié E, Mankoff D. 18F-FDG PET/CT for staging and restaging of breast cancer. J Nucl Med. 2016;57:17S–26S.CrossRef
4.
go back to reference Paydary K, Seraj SM, Zadeh MZ, et al. The evolving role of FDG-PET/CT in the diagnosis, staging, and treatment of breast cancer. Mol Imaging Biol. 2019;21:1–10.CrossRef Paydary K, Seraj SM, Zadeh MZ, et al. The evolving role of FDG-PET/CT in the diagnosis, staging, and treatment of breast cancer. Mol Imaging Biol. 2019;21:1–10.CrossRef
5.
go back to reference Paidpally V, Chirindel A, Chung CH, et al. FDG volumetric parameters and survival outcomes after definitive chemoradiotherapy in patients with recurrent head and neck squamous cell carcinoma. Am J Roentgenol. 2014;203:W139–45.CrossRef Paidpally V, Chirindel A, Chung CH, et al. FDG volumetric parameters and survival outcomes after definitive chemoradiotherapy in patients with recurrent head and neck squamous cell carcinoma. Am J Roentgenol. 2014;203:W139–45.CrossRef
6.
go back to reference Lemarignier C, Di Fiore F, Marre C, et al. Pretreatment metabolic tumour volume is predictive of disease-free survival and overall survival in patients with oesophageal squamous cell carcinoma. Eur J Nucl Med Mol Imaging. 2014;41:2008–16.CrossRef Lemarignier C, Di Fiore F, Marre C, et al. Pretreatment metabolic tumour volume is predictive of disease-free survival and overall survival in patients with oesophageal squamous cell carcinoma. Eur J Nucl Med Mol Imaging. 2014;41:2008–16.CrossRef
7.
go back to reference Hyun SH, Ahn HK, Park YH, et al. Volume-based metabolic tumor response to neoadjuvant chemotherapy is associated with an increased risk of recurrence in breast cancer. Radiology. 2015;275:235–44.CrossRef Hyun SH, Ahn HK, Park YH, et al. Volume-based metabolic tumor response to neoadjuvant chemotherapy is associated with an increased risk of recurrence in breast cancer. Radiology. 2015;275:235–44.CrossRef
8.
go back to reference Barrington SF, Kluge R. FDG PET for therapy monitoring in Hodgkin and non-Hodgkin lymphomas. Eur J Nucl Med Mol Imaging. 2017;44:97–110.CrossRef Barrington SF, Kluge R. FDG PET for therapy monitoring in Hodgkin and non-Hodgkin lymphomas. Eur J Nucl Med Mol Imaging. 2017;44:97–110.CrossRef
9.
go back to reference Joo Hyun O, Lodge MA, Wahl RL. Practical PERCIST: a simplified guide to PET response criteria in solid tumors 1.0. Radiology. 2016;280:576–84.CrossRef Joo Hyun O, Lodge MA, Wahl RL. Practical PERCIST: a simplified guide to PET response criteria in solid tumors 1.0. Radiology. 2016;280:576–84.CrossRef
10.
go back to reference Litjens G, Kooi T, Bejnordi BE, et al. A survey on deep learning in medical image analysis. Med Image Anal. 2017;42:60–88.CrossRef Litjens G, Kooi T, Bejnordi BE, et al. A survey on deep learning in medical image analysis. Med Image Anal. 2017;42:60–88.CrossRef
11.
go back to reference Huynh BQ, Li H, Giger ML. Digital mammographic tumor classification using transfer learning from deep convolutional neural networks. J Med Imaging. 2016;3:034501.CrossRef Huynh BQ, Li H, Giger ML. Digital mammographic tumor classification using transfer learning from deep convolutional neural networks. J Med Imaging. 2016;3:034501.CrossRef
12.
go back to reference Larson DB, Chen MC, Lungren MP, Halabi SS, Stence NV, Langlotz CP. Performance of a deep-learning neural network model in assessing skeletal maturity on pediatric hand radiographs. Radiology. 2018;287:313–22.CrossRef Larson DB, Chen MC, Lungren MP, Halabi SS, Stence NV, Langlotz CP. Performance of a deep-learning neural network model in assessing skeletal maturity on pediatric hand radiographs. Radiology. 2018;287:313–22.CrossRef
13.
go back to reference Rajpurkar P, Irvin J, Ball RL, et al. Deep learning for chest radiograph diagnosis: a retrospective comparison of the CheXNeXt algorithm to practicing radiologists. PLoS Med. 2018;15:1–17.CrossRef Rajpurkar P, Irvin J, Ball RL, et al. Deep learning for chest radiograph diagnosis: a retrospective comparison of the CheXNeXt algorithm to practicing radiologists. PLoS Med. 2018;15:1–17.CrossRef
14.
go back to reference Bien N, Rajpurkar P, Ball RL, et al. Deep-learning-assisted diagnosis for knee magnetic resonance imaging: development and retrospective validation of MRNet. PLoS Med. 2018;15:1–19.CrossRef Bien N, Rajpurkar P, Ball RL, et al. Deep-learning-assisted diagnosis for knee magnetic resonance imaging: development and retrospective validation of MRNet. PLoS Med. 2018;15:1–19.CrossRef
15.
go back to reference Sibille L, Seifert R, Avramovic N, et al. 18 F-FDG PET/CT uptake classification in lymphoma and lung cancer by using deep convolutional neural networks. Radiology. 2010;294(2): p. 445–452. Sibille L, Seifert R, Avramovic N, et al. 18 F-FDG PET/CT uptake classification in lymphoma and lung cancer by using deep convolutional neural networks. Radiology. 2010;294(2): p. 445–452.
16.
go back to reference Lapuschkin S, Wäldchen S, Binder A, Montavon G, Samek W, Müller KR. Unmasking clever Hans predictors and assessing what machines really learn. Nat Commun. 2019;10:1–8.CrossRef Lapuschkin S, Wäldchen S, Binder A, Montavon G, Samek W, Müller KR. Unmasking clever Hans predictors and assessing what machines really learn. Nat Commun. 2019;10:1–8.CrossRef
17.
go back to reference Baskerville JR. Short report: what can educators learn from clever Hans the math horse?: education and training. EMA – Emerg Med Australas. 2010;22:330–1.CrossRef Baskerville JR. Short report: what can educators learn from clever Hans the math horse?: education and training. EMA – Emerg Med Australas. 2010;22:330–1.CrossRef
18.
go back to reference Boellaard R, Delgado-Bolton R, Oyen WJG, 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 WJG, 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
19.
go back to reference Armstrong AJ, Anand A, Edenbrandt L, et al. Phase 3 assessment of the automated bone scan index as a prognostic imaging biomarker of overall survival in men with metastatic castration-resistant prostate cancer a secondary analysis of a randomized clinical trial. JAMA Oncol. 2018;4:944–51.CrossRef Armstrong AJ, Anand A, Edenbrandt L, et al. Phase 3 assessment of the automated bone scan index as a prognostic imaging biomarker of overall survival in men with metastatic castration-resistant prostate cancer a secondary analysis of a randomized clinical trial. JAMA Oncol. 2018;4:944–51.CrossRef
20.
go back to reference Turck N, Vutskits L, Sanchez-Pena P, et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics. 2011;8:12–77. Turck N, Vutskits L, Sanchez-Pena P, et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics. 2011;8:12–77.
21.
go back to reference Gönen M, Heller G. Concordance probability and discriminatory power in proportional hazards regression. Biometrika. 2005;92:965–70.CrossRef Gönen M, Heller G. Concordance probability and discriminatory power in proportional hazards regression. Biometrika. 2005;92:965–70.CrossRef
22.
go back to reference Nensa F, Demircioglu A, Rischpler C. Artificial intelligence in nuclear medicine. J Nucl Med. 2019;60:29S–37S.CrossRef Nensa F, Demircioglu A, Rischpler C. Artificial intelligence in nuclear medicine. J Nucl Med. 2019;60:29S–37S.CrossRef
23.
go back to reference Meignan M, Cottereau AS, Versari A, et al. Baseline metabolic tumor volume predicts outcome in high-tumor-burden follicular lymphoma: a pooled analysis of three multicenter studies. J Clin Oncol. 2016;34:3618–26.CrossRef Meignan M, Cottereau AS, Versari A, et al. Baseline metabolic tumor volume predicts outcome in high-tumor-burden follicular lymphoma: a pooled analysis of three multicenter studies. J Clin Oncol. 2016;34:3618–26.CrossRef
24.
go back to reference Salavati A, Duan F, Snyder BS, et al. Optimal FDG PET/CT volumetric parameters for risk stratification in patients with locally advanced non-small cell lung cancer: results from the ACRIN 6668/RTOG 0235 trial. Eur J Nucl Med Mol Imaging. 2017;44:1969–83.CrossRef Salavati A, Duan F, Snyder BS, et al. Optimal FDG PET/CT volumetric parameters for risk stratification in patients with locally advanced non-small cell lung cancer: results from the ACRIN 6668/RTOG 0235 trial. Eur J Nucl Med Mol Imaging. 2017;44:1969–83.CrossRef
25.
go back to reference Reiter JG, Hung WT, Lee IH, et al. Lymph node metastases develop through a wider evolutionary bottleneck than distant metastases. Nat Genet. 2020;52(7): p. 692–700. Reiter JG, Hung WT, Lee IH, et al. Lymph node metastases develop through a wider evolutionary bottleneck than distant metastases. Nat Genet. 2020;52(7): p. 692–700.
26.
go back to reference Hu Z, Ding J, Ma Z, et al. Quantitative evidence for early metastatic seeding in colorectal cancer. Nat Genet. 2019;51:1113–22.CrossRef Hu Z, Ding J, Ma Z, et al. Quantitative evidence for early metastatic seeding in colorectal cancer. Nat Genet. 2019;51:1113–22.CrossRef
27.
go back to reference Capobianco N, Meignan MA, Cottereau A-S, et al. Deep learning FDG uptake classification enables total metabolic tumor volume estimation in diffuse large B-cell lymphoma. J Nucl Med. 2020;57:jnumed.120.242412. Capobianco N, Meignan MA, Cottereau A-S, et al. Deep learning FDG uptake classification enables total metabolic tumor volume estimation in diffuse large B-cell lymphoma. J Nucl Med. 2020;57:jnumed.120.242412.
28.
go back to reference Wang R, Zhu Y, Liu X, Liao X, He J, Niu L. The clinicopathological features and survival outcomes of patients with different metastatic sites in stage IV breast cancer. BMC Cancer. 2019;19:1091.CrossRef Wang R, Zhu Y, Liu X, Liao X, He J, Niu L. The clinicopathological features and survival outcomes of patients with different metastatic sites in stage IV breast cancer. BMC Cancer. 2019;19:1091.CrossRef
Metadata
Title
Just another “Clever Hans”? Neural networks and FDG PET-CT to predict the outcome of patients with breast cancer
Authors
Manuel Weber
David Kersting
Lale Umutlu
Michael Schäfers
Christoph Rischpler
Wolfgang P. Fendler
Irène Buvat
Ken Herrmann
Robert Seifert
Publication date
01-09-2021
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 10/2021
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-021-05270-x

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