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

01-05-2020 | NSCLC | Original Article

Radiomics of 18F-FDG PET/CT images predicts clinical benefit of advanced NSCLC patients to checkpoint blockade immunotherapy

Authors: Wei Mu, Ilke Tunali, Jhanelle E. Gray, Jin Qi, Matthew B. Schabath, Robert J. Gillies

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 5/2020

Login to get access

Abstract

Introduction

Immunotherapy has improved outcomes for patients with non-small cell lung cancer (NSCLC), yet durable clinical benefit (DCB) is experienced in only a fraction of patients. Here, we test the hypothesis that radiomics features from baseline pretreatment 18F-FDG PET/CT scans can predict clinical outcomes of NSCLC patients treated with checkpoint blockade immunotherapy.

Methods

This study included 194 patients with histologically confirmed stage IIIB-IV NSCLC with pretreatment PET/CT images. Radiomics features were extracted from PET, CT, and PET+CT fusion images based on minimum Kullback–Leibler divergence (KLD) criteria. The radiomics features from 99 retrospective patients were used to train a multiparametric radiomics signature (mpRS) to predict DCB using an improved least absolute shrinkage and selection operator (LASSO) method, which was subsequently validated in both retrospective (N = 47) and prospective test cohorts (N = 48). Using these cohorts, the mpRS was also used to predict progression-free survival (PFS) and overall survival (OS) by training nomogram models using multivariable Cox regression analyses with additional clinical characteristics incorporated.

Results

The mpRS could predict patients who will receive DCB, with areas under receiver operating characteristic curves (AUCs) of 0.86 (95%CI 0.79–0.94), 0.83 (95%CI 0.71–0.94), and 0.81 (95%CI 0.68–0.92) in the training, retrospective test, and prospective test cohorts, respectively. In the same three cohorts, respectively, nomogram models achieved C-indices of 0.74 (95%CI 0.68–0.80), 0.74 (95%CI 0.66–0.82), and 0.77 (95%CI 0.69–0.84) to predict PFS and C-indices of 0.83 (95%CI 0.77–0.88), 0.83 (95%CI 0.71–0.94), and 0.80 (95%CI 0.69–0.91) to predict OS.

Conclusion

PET/CT-based signature can be used prior to initiation of immunotherapy to identify NSCLC patients most likely to benefit from immunotherapy. As such, these data may be leveraged to improve more precise and individualized decision support in the treatment of patients with advanced NSCLC.
Appendix
Available only for authorised users
Literature
1.
go back to reference Torre LA, Siegel RL, Jemal A. Lung cancer statistics. Lung cancer and personalized medicine. Springer; 2016. p. 1–19. Torre LA, Siegel RL, Jemal A. Lung cancer statistics. Lung cancer and personalized medicine. Springer; 2016. p. 1–19.
2.
go back to reference Jamal-Hanjani M, Wilson GA, McGranahan N, Birkbak NJ, Watkins TBK, Veeriah S, et al. Tracking the evolution of non–small-cell lung cancer. N Engl J Med. 2017;376(22):2109–21.CrossRef Jamal-Hanjani M, Wilson GA, McGranahan N, Birkbak NJ, Watkins TBK, Veeriah S, et al. Tracking the evolution of non–small-cell lung cancer. N Engl J Med. 2017;376(22):2109–21.CrossRef
4.
go back to reference Rizvi NA, Mazières J, Planchard D, Stinchcombe TE, Dy GK, Antonia SJ, et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 2015;16(3):257–65.CrossRef Rizvi NA, Mazières J, Planchard D, Stinchcombe TE, Dy GK, Antonia SJ, et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 2015;16(3):257–65.CrossRef
5.
go back to reference Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer. New Engl J Med. 2016;375(19):1823–33.CrossRef Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer. New Engl J Med. 2016;375(19):1823–33.CrossRef
7.
go back to reference Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non–small-cell lung cancer. New Engl J Med. 2015;372(21):2018–28.CrossRef Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non–small-cell lung cancer. New Engl J Med. 2015;372(21):2018–28.CrossRef
8.
go back to reference Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti–PD-1 antibody in cancer. New Engl J Med. 2012;366(26):2443–54.CrossRef Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti–PD-1 antibody in cancer. New Engl J Med. 2012;366(26):2443–54.CrossRef
9.
go back to reference Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, Von Pawel J, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389(10066):255–65.CrossRef Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, Von Pawel J, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389(10066):255–65.CrossRef
10.
go back to reference Herbst RS, Soria J-C, Kowanetz M, Fine GD, Hamid O, Gordon MS, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515(7528):563.CrossRef Herbst RS, Soria J-C, Kowanetz M, Fine GD, Hamid O, Gordon MS, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515(7528):563.CrossRef
12.
go back to reference Meng X, Huang Z, Teng F, Xing L, Yu J. Predictive biomarkers in PD-1/PD-L1 checkpoint blockade immunotherapy. Cancer Treat Rev. 2015;41(10):868–76.CrossRef Meng X, Huang Z, Teng F, Xing L, Yu J. Predictive biomarkers in PD-1/PD-L1 checkpoint blockade immunotherapy. Cancer Treat Rev. 2015;41(10):868–76.CrossRef
13.
go back to reference Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer. Science. 2015;348(6230):124–8.CrossRef Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer. Science. 2015;348(6230):124–8.CrossRef
14.
go back to reference 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
15.
go back to reference Beukinga RJ, Hulshoff JB, Mul VE, Noordzij W, Kats-Ugurlu G, Slart RH, et al. Prediction of response to neoadjuvant chemotherapy and radiation therapy with baseline and restaging 18F-FDG PET imaging biomarkers in patients with esophageal cancer. Radiology. 2018;287(3):983–92 172229.CrossRef Beukinga RJ, Hulshoff JB, Mul VE, Noordzij W, Kats-Ugurlu G, Slart RH, et al. Prediction of response to neoadjuvant chemotherapy and radiation therapy with baseline and restaging 18F-FDG PET imaging biomarkers in patients with esophageal cancer. Radiology. 2018;287(3):983–92 172229.CrossRef
19.
go back to reference Campesato LF, Barroso-Sousa R, Jimenez L, Correa BR, Sabbaga J, Hoff PM, et al. Comprehensive cancer-gene panels can be used to estimate mutational load and predict clinical benefit to PD-1 blockade in clinical practice. Oncotarget. 2015;6(33):34221–7.CrossRef Campesato LF, Barroso-Sousa R, Jimenez L, Correa BR, Sabbaga J, Hoff PM, et al. Comprehensive cancer-gene panels can be used to estimate mutational load and predict clinical benefit to PD-1 blockade in clinical practice. Oncotarget. 2015;6(33):34221–7.CrossRef
20.
go back to reference Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.CrossRef Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.CrossRef
21.
go back to reference Kullback S, Leibler RA. On information and sufficiency. Ann Math Stat. 1951;22(1):79–86.CrossRef Kullback S, Leibler RA. On information and sufficiency. Ann Math Stat. 1951;22(1):79–86.CrossRef
22.
go back to reference Tibshirani R. Regression shrinkage and selection via the lasso. J R Stat Soc Ser B Methodol. 1996;58(1):267–88. Tibshirani R. Regression shrinkage and selection via the lasso. J R Stat Soc Ser B Methodol. 1996;58(1):267–88.
23.
go back to reference Crivellaro C, Signorelli M, Guerra L, De Ponti E, Buda A, Dolci C, et al. 18F-FDG PET/CT can predict nodal metastases but not recurrence in early stage uterine cervical cancer. Gynecol Oncol. 2012;127(1):131–5.CrossRef Crivellaro C, Signorelli M, Guerra L, De Ponti E, Buda A, Dolci C, et al. 18F-FDG PET/CT can predict nodal metastases but not recurrence in early stage uterine cervical cancer. Gynecol Oncol. 2012;127(1):131–5.CrossRef
24.
go back to reference Taniguchi K, Okami J, Kodama K, Higashiyama M, Kato K. Intratumor heterogeneity of epidermal growth factor receptor mutations in lung cancer and its correlation to the response to gefitinib. Cancer Sci. 2008;99(5):929–35.CrossRef Taniguchi K, Okami J, Kodama K, Higashiyama M, Kato K. Intratumor heterogeneity of epidermal growth factor receptor mutations in lung cancer and its correlation to the response to gefitinib. Cancer Sci. 2008;99(5):929–35.CrossRef
25.
go back to reference Fitzgerald M, Saville BR, Lewis RJ. Decision curve analysis. Jama. 2015;313(4):409–10.CrossRef Fitzgerald M, Saville BR, Lewis RJ. Decision curve analysis. Jama. 2015;313(4):409–10.CrossRef
26.
go back to reference Gambhir SS. Molecular imaging of cancer with positron emission tomography. Nat Rev Cancer. 2002;2(9):683.CrossRef Gambhir SS. Molecular imaging of cancer with positron emission tomography. Nat Rev Cancer. 2002;2(9):683.CrossRef
28.
go back to reference Wu J, Aguilera T, Shultz D, Gudur M, Rubin DL, Loo BW Jr, et al. Early-stage non–small cell lung cancer: quantitative imaging characteristics of 18F fluorodeoxyglucose PET/CT allow prediction of distant metastasis. Radiology. 2016;281(1):270–8.CrossRef Wu J, Aguilera T, Shultz D, Gudur M, Rubin DL, Loo BW Jr, et al. Early-stage non–small cell lung cancer: quantitative imaging characteristics of 18F fluorodeoxyglucose PET/CT allow prediction of distant metastasis. Radiology. 2016;281(1):270–8.CrossRef
29.
go back to reference Vallières M, Freeman CR, Skamene SR, El Naqa I. A radiomics model from joint FDG-PET and MRI texture features for the prediction of lung metastases in soft-tissue sarcomas of the extremities. Phys Med Biol. 2015;60(14):5471.CrossRef Vallières M, Freeman CR, Skamene SR, El Naqa I. A radiomics model from joint FDG-PET and MRI texture features for the prediction of lung metastases in soft-tissue sarcomas of the extremities. Phys Med Biol. 2015;60(14):5471.CrossRef
30.
go back to reference Carvalho S, Leijenaar R, Troost E, van Elmpt W, Muratet J-P, Denis F, et al. Early variation of FDG-PET radiomics features in NSCLC is related to overall survival-the “delta radiomics” concept. Radiother Oncol. 2016;118:S20–S1.CrossRef Carvalho S, Leijenaar R, Troost E, van Elmpt W, Muratet J-P, Denis F, et al. Early variation of FDG-PET radiomics features in NSCLC is related to overall survival-the “delta radiomics” concept. Radiother Oncol. 2016;118:S20–S1.CrossRef
31.
go back to reference Oikonomou A, Khalvati F, Tyrrell PN, Haider MA, Tarique U, Jimenez-Juan L, et al. Radiomics analysis at PET/CT contributes to prognosis of recurrence and survival in lung cancer treated with stereotactic body radiotherapy. Sci Rep. 2018;8(1):4003.CrossRef Oikonomou A, Khalvati F, Tyrrell PN, Haider MA, Tarique U, Jimenez-Juan L, et al. Radiomics analysis at PET/CT contributes to prognosis of recurrence and survival in lung cancer treated with stereotactic body radiotherapy. Sci Rep. 2018;8(1):4003.CrossRef
32.
go back to reference Kirienko M, Cozzi L, Antunovic L, Lozza L, Fogliata A, Voulaz E, et al. Prediction of disease-free survival by the PET/CT radiomic signature in non-small cell lung cancer patients undergoing surgery. Eur J Nucl Med Mol Imaging. 2018;45(2):207–17.CrossRef Kirienko M, Cozzi L, Antunovic L, Lozza L, Fogliata A, Voulaz E, et al. Prediction of disease-free survival by the PET/CT radiomic signature in non-small cell lung cancer patients undergoing surgery. Eur J Nucl Med Mol Imaging. 2018;45(2):207–17.CrossRef
36.
go back to reference Bar-Shalom R, Yefremov N, Guralnik L, Gaitini D, Frenkel A, Kuten A, et al. Clinical performance of PET/CT in evaluation of cancer: additional value for diagnostic imaging and patient management. J Nucl Med. 2003;44(8):1200–9.PubMed Bar-Shalom R, Yefremov N, Guralnik L, Gaitini D, Frenkel A, Kuten A, et al. Clinical performance of PET/CT in evaluation of cancer: additional value for diagnostic imaging and patient management. J Nucl Med. 2003;44(8):1200–9.PubMed
37.
go back to reference Champiat S, Dercle L, Ammari S, Massard C, Hollebecque A, Postel-Vinay S, et al. Hyperprogressive disease is a new pattern of progression in cancer patients treated by anti-PD-1/PD-L1. Clin Cancer Res. 2017;23(8):1920–8.CrossRef Champiat S, Dercle L, Ammari S, Massard C, Hollebecque A, Postel-Vinay S, et al. Hyperprogressive disease is a new pattern of progression in cancer patients treated by anti-PD-1/PD-L1. Clin Cancer Res. 2017;23(8):1920–8.CrossRef
38.
go back to reference Saeed-Vafa D, Bravo R, Dean JA, El-Kenawi A, Père NM, Strobl M et al. Combining radiomics and mathematical modeling to elucidate mechanisms of resistance to immune checkpoint blockade in non-small cell lung cancer. bioRxiv. 2017:190561. Saeed-Vafa D, Bravo R, Dean JA, El-Kenawi A, Père NM, Strobl M et al. Combining radiomics and mathematical modeling to elucidate mechanisms of resistance to immune checkpoint blockade in non-small cell lung cancer. bioRxiv. 2017:190561.
41.
go back to reference 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(4):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(4):569–76.CrossRef
42.
go back to reference Kaira K, Higuchi T, Naruse I, Arisaka Y, Tokue A, Altan B, et al. Metabolic activity by 18F–FDG-PET/CT is predictive of early response after nivolumab in previously treated NSCLC. Eur J Nucl Med Mol Imaging. 2018;45(1):56–66.CrossRef Kaira K, Higuchi T, Naruse I, Arisaka Y, Tokue A, Altan B, et al. Metabolic activity by 18F–FDG-PET/CT is predictive of early response after nivolumab in previously treated NSCLC. Eur J Nucl Med Mol Imaging. 2018;45(1):56–66.CrossRef
Metadata
Title
Radiomics of 18F-FDG PET/CT images predicts clinical benefit of advanced NSCLC patients to checkpoint blockade immunotherapy
Authors
Wei Mu
Ilke Tunali
Jhanelle E. Gray
Jin Qi
Matthew B. Schabath
Robert J. Gillies
Publication date
01-05-2020
Publisher
Springer Berlin Heidelberg
Keywords
NSCLC
NSCLC
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 5/2020
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-019-04625-9

Other articles of this Issue 5/2020

European Journal of Nuclear Medicine and Molecular Imaging 5/2020 Go to the issue