Skip to main content

Advertisement

Log in

Metabolic activity by 18F–FDG-PET/CT is predictive of early response after nivolumab in previously treated NSCLC

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Background

Nivolumab, an anti-programmed death-1 (PD-1) antibody, is administered in patients with previously treated non-small cell lung cancer. However, little is known about the established biomarker predicting the efficacy of nivolumab. Here, we conducted a preliminary study to investigate whether 18F–FDG-PET/CT could predict the therapeutic response of nivolumab at the early phase.

Methods

Twenty-four patients were enrolled in this study. 18F–FDG-PET/CT was carried out before and 1 month after nivolumab therapy. SUVmax, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were calculated. Immunohistochemical analysis of PD-L1 expression and tumour-infiltrating lymphocytes was conducted.

Results

Among all patients, a partial metabolic response to nivolumab was observed in 29% on SUVmax, 25% on MTV, and 33% on TLG, whereas seven (29%) patients achieved a partial response (PR) based on RECIST v1.1. The predictive probability of PR (100% vs. 29%, p = 0.021) and progressive disease (100% vs. 22.2%, p = 0.002) at 1 month after nivolumab initiation was significantly higher in 18F–FDG on PET/CT than in CT scans. Multivariate analysis confirmed that 18F–FDG uptake after administration of nivolumab was an independent prognostic factor. PD-L1 expression and nivolumab plasma concentration could not precisely predict the early therapeutic efficacy of nivolumab.

Conclusion

Metabolic response by 18F–FDG was effective in predicting efficacy and survival at 1 month after nivolumab treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Mountain CF. Revisions in the international system for staging lung cancer. Chest. 1997;111:1719–7.

    Google Scholar 

  2. Pfister DG, Johnson DH, Azzoli CG, et al. American Society of Clinical Oncology treated of unresectable non-small-cell lung cancer guildeline: update 2003. J Clin Oncol. 2004;22:330–53.

    Article  Google Scholar 

  3. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus Docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:123–35.

    Article  CAS  Google Scholar 

  4. Borghaei H, Paz-Ares L, Hom L, et al. Nivolumab versus Docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627–39.

    Article  CAS  Google Scholar 

  5. Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1 positive non-small-cell lung cancer. N Engl J Med. 2016;375:1823–33.

    Article  CAS  Google Scholar 

  6. Pieterman RM, van Putten JW, Meuzelaar JJ, et al. Preoperative staging of non-small-cell lung cancer with positron-emission tomography. N Engl J Med. 2000;343:254–61.

    Article  CAS  Google Scholar 

  7. Lardinois D, Weder W, Hany TF, et al. Staging of non-small-cell lung cancer with integrated positron- emission tomography and computed tomography. N Engl J Med. 2003;348:2500–7.

    Article  Google Scholar 

  8. Moon SH, Cho SH, Park LC, et al. Metabolic response evaluated by 18F-FDG PET/CT as a potential screening tool in identifying a subgroup of patients with advanced non-small cell lung cancer for immediate maintenance therapy after first-line chemotherapy. Eur J Nucl Med Mol Imaging. 2013;40:1005–13.

    Article  CAS  Google Scholar 

  9. Wahl RL, Jacene H, Kasamon Y, et al. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50(Suppl 1):122S–5S.

    Article  CAS  Google Scholar 

  10. Sunaga N, Oriuchi N, Kaira K, et al. Usefulness of FDG-PET for early prediction of the response to gefitinib in non-small cell lung cancer. Lung Cancer. 2008;59:203–10.

    Article  Google Scholar 

  11. Kaira K, Endo M, Abe M, et al. Biologic correlation of 2-[18F]-fluoro-2-deoxy-D-glucose uptake on positron emission tomography in thymic epithelial tumors. J Clin Oncol. 2010;28:3746–53.

    Article  CAS  Google Scholar 

  12. Chang YL, Yang CY, Lin MW, et al. High co-expression of PD-L1 and HIF-1α correlates with tumour necrosis in pulmonary pleomorphic carcinoma. Eur J Cancer. 2016;60:125–35.

    Article  CAS  Google Scholar 

  13. Ruf M, Moch H, Schraml P. PD-L1 expression is regulated by hypoxia inducible factor in clear renal cell carcinoma. Int J Cancer. 2016;139:396–403.

    Article  CAS  Google Scholar 

  14. Lopci E, Toschi L, Grizzi F, et al. Cprrelation of metabolic information on FDG-PET with tissue expression of immune markers in patients with non-small cell lung cancer (NSCLC) who are candidates for upfront surgery. Eur J Nucl Med Mol Imaging. 2016;43:1954–61.

    Article  CAS  Google Scholar 

  15. Im HJ, Pak K, Cheon GJ, et al. Prognostic value of volumetric parameters of (18)F-FDG PET in non-small-cell lung cancer: a meta-analysis. Eur J Nucl Med Mol Imaging. 2015;42:241–51.

    Article  CAS  Google Scholar 

  16. Chen J, Jiang CC, Jin L, et al. Regulation of PD-1:a novel role of pro-survival signalling in cancer. Ann Oncol. 2016;27:409–16.

    Article  CAS  Google Scholar 

  17. Noman MZ, Desantis G, Janji B, et al. PD-L1 is a novel direct target of HIF-1α, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med. 2014;211:781–90.

    Article  CAS  Google Scholar 

  18. Kaira K, Serizawa M, Koh Y, et al. Biological significance of 18F-FDG uptake on PET in patients with non-small-cell lung cancer. Lung Cancer. 2014;83:197–204.

    Article  Google Scholar 

  19. Higuchi M, Owada Y, Inoue T, et al. FDG-PET in the evaluation of response to nivolumab in recurrent non-small-cell lung cancer. World J Surg Oncol. 2016;14:238.

    Article  Google Scholar 

  20. Sachpekidis C, Hassel JC, Dimitrakopoulou-Strauss A. 18F-FDG PET/CT reveals disease remission in a patient with Ipilimumab-refractory advanced melanoma treated with Pembrolizumab. Clin Nucl Med. 2016;41:156–8.

    Article  Google Scholar 

  21. England CG, Ehlerding EB, Hernandez R, et al. Preclinical pharmacokinetics and biodistribution studies of 89Zr-labeled Pembrolizumab. J Nucl Med. 2017;58:162–8.

    Article  CAS  Google Scholar 

  22. Giglio BC, Fei H, Wang M, et al. Synthesis of 5-[18F]Fluoro-α-methyl tryptophan: new Trp based PET agents. Theranostics. 2017;7:1524–30.

    Article  CAS  Google Scholar 

  23. Pauleit D, Stoffels G, Schaden W, et al. PET with O-(2-18F-fluoroethyl)-L-tyrosine in peripheral tumors: first clinical results. J Nucl Med. 2005;46:411–6.

    CAS  Google Scholar 

  24. Jager PL, Groen HJM, van der Leest A, et al. L-3-123I-iodo-a-methyl-L-tyrosine SPECT in non-small cell lung cancer: preliminary observations. J Nucl Med. 2001;42:579–85.

    CAS  Google Scholar 

  25. Kaira K, Oriuchi N, Otani Y, et al. Fluorine-18-α-methyltyrosine positron emission tomography for diagnosis and staging of lung cancer: a clinicopathologic study. Clin Cancer Res. 2007;13:6369–78.

    Article  CAS  Google Scholar 

  26. Kaira K, Oriuchi N, Otani Y, et al. Diagnostic usefulness of fluorine-18-alpha-methyltyrosine positron emission tomography in combination with 18F-fluorodeoxyglucose in sarcoidosis patients. Chest. 2007;131:1019–27.

    Article  Google Scholar 

Download references

Acknowledgements

We thank Ms. Yuka Matsui for her technical assistance during the manuscript submission. We deeply appreciate the help provided by Ms. Yoko Tokumitsu of the Department of Outpatient Chemotherapy Center, Hidaka Hospital, Drs. Toshitaka Maeno, Kenichiro Hara, Yasuhiko Koga, and Akira Ono of the Department of Respiratory Medicine, and Drs. Toshiki Yajima and Takayuki Kosaka of the Department of Respiratory Surgery, Gunma University Hospital, for data collection and clinical advice.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kyoichi Kaira.

Ethics declarations

Conflict of interest

KK has received research grants and speaker honoraria from Ono Pharmaceutical Company and Bristol-Myers Company. All remaining authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Electronic supplementary material

ESM 1

(PPTX 112 kb)

ESM 2

(DOCX 24 kb)

ESM 3

(DOCX 18 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kaira, K., Higuchi, T., Naruse, I. 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 45, 56–66 (2018). https://doi.org/10.1007/s00259-017-3806-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-017-3806-1

Keywords

Navigation