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

  • Kyoichi Kaira
  • Tetsuya Higuchi
  • Ichiro Naruse
  • Yukiko Arisaka
  • Azusa Tokue
  • Bolag Altan
  • Satoshi Suda
  • Akira Mogi
  • Kimihiro Shimizu
  • Noriaki Sunaga
  • Takeshi Hisada
  • Shigehisa Kitano
  • Hideru Obinata
  • Takehiko Yokobori
  • Keita Mori
  • Masahiko Nishiyama
  • Yoshihito Tsushima
  • Takayuki Asao
Original Article

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.

Keywords

FDG-PET Nivolumab Pd-L1 Lung cancer Early response 

Notes

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.

Compliance with ethical standards

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.

Supplementary material

259_2017_3806_MOESM1_ESM.pptx (112 kb)
ESM 1 (PPTX 112 kb)
259_2017_3806_MOESM2_ESM.docx (24 kb)
ESM 2 (DOCX 24 kb)
259_2017_3806_MOESM3_ESM.docx (19 kb)
ESM 3 (DOCX 18 kb)

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Kyoichi Kaira
    • 1
  • Tetsuya Higuchi
    • 2
  • Ichiro Naruse
    • 3
  • Yukiko Arisaka
    • 2
  • Azusa Tokue
    • 2
  • Bolag Altan
    • 1
  • Satoshi Suda
    • 4
  • Akira Mogi
    • 5
  • Kimihiro Shimizu
    • 5
  • Noriaki Sunaga
    • 6
  • Takeshi Hisada
    • 7
  • Shigehisa Kitano
    • 8
  • Hideru Obinata
    • 9
  • Takehiko Yokobori
    • 10
  • Keita Mori
    • 11
  • Masahiko Nishiyama
    • 12
  • Yoshihito Tsushima
    • 2
    • 13
  • Takayuki Asao
    • 9
  1. 1.Department of Oncology Clinical DevelopmentGunma University Graduate School of MedicineMaebashiJapan
  2. 2.Department of Diagnostic Radiology and Nuclear MedicineGunma University Graduate School of MedicineMaebashiJapan
  3. 3.Department of Respiratory MedicineHidaka HospitalHidakaJapan
  4. 4.Department of RadiologyHidaka HospitalHidakaJapan
  5. 5.Department of General Surgical ScienceGunma University Graduate School of MedicineMaebashiJapan
  6. 6.Oncology CenterGunma University HospitalMaebashiJapan
  7. 7.Department of Respiratory MedicineGunma University HospitalMaebashiJapan
  8. 8.Department of Experimental TherapeuticsNational Cancer Center HospitalTokyoJapan
  9. 9.Big Data Center for Integrative AnalysisGunma University Initiative for Advanced ResearchMaebashiJapan
  10. 10.Division of Integrated Oncology Research, Research Program for Omics-based Medical ScienceGunma University Initiative for Advanced ResearchMaebashiJapan
  11. 11.Clinical Research Support Center, Shizuoka Cancer CenterSuntou-gunJapan
  12. 12.Department of Molecular Pharmacology and OncologyGunma University Graduate School of MedicineMaebashiJapan
  13. 13.Research Program for Diagnostic and Molecular Imaging, Division of Integrated Oncology ResearchGunma University Initiative for Advanced Research (GIAR)MaebashiJapan

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