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Usefulness of [18F]fluorodeoxyglucose PET/CT for evaluating the PD-L1 status in nasopharyngeal carcinoma

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

To explore the relationship between [18F]fluorodeoxyglucose (18F-FDG uptake) and PD-L1 expression and determine the usefulness of 18F-FDG PET/CT for evaluating the PD-L1 status in tumour cells (TCs) and tumour-infiltrating immune cells (TIICs) in patients with nasopharyngeal carcinoma (NPC).

Methods

We retrospectively evaluated the records of 84 eligible patients who received an initial histopathological diagnosis of NPC between December 2016 and March 2019. All tissue specimens and PET/CT images were collected prior to treatment. High PD-L1 expression in TCs and TIICs was defined as ≥ 50% of stained cells.

Results

There was a significant difference in 18F-FDG uptake according to the PD-L1 status in TCs and TIICs. Univariate analysis showed that PD-L1 expression in TCs was associated with tumour maximum standardized uptake value (SUVmax) (P < 0.001), primary tumour total lesion glycolysis (TLG; P < 0.001), and T stage (P = 0.044), but not with plasma Epstein-Barr virus (EBV) load (P = 0.816), whereas PD-L1 expression in TIICs was related to SUVmax (P = 0.011), TLG (P = 0.001), T stage (P = 0.028), and plasma EBV load (P = 0.003). In multivariate logistic regression, PD-L1 expression in TCs was positively associated with SUVmax (P = 0.003) and TLG (P = 0.001), and in TIICs, negatively associated with SUVmax (P = 0.038) and plasma EBV load (P = 0.025).

Conclusions

18F-FDG uptake in NPC lesions was positively correlated with PD-L1 expression in TCs and negatively correlated with PD-L1 expression in TIICs. Thus, 18F-FDG PET/CT may be useful for evaluating the PD-L1 status in patients with NPC.

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References

  1. Chua MLK, et al. Nasopharyngeal carcinoma. Lancet. 2016;387(10022):1012–24.

    Article  Google Scholar 

  2. Yu MC, Yuan JM. Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol. 2002;12(6):421–9.

    Article  Google Scholar 

  3. Chang ET, Adami HO. The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomark Prev. 2006;15(10):1765–77.

    Article  CAS  Google Scholar 

  4. Chen QY, et al. Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: phase III randomized trial. J Natl Cancer Inst. 2011;103(23):1761–70.

    Article  Google Scholar 

  5. Lee AW, et al. Management of nasopharyngeal carcinoma: current practice and future perspective. J Clin Oncol. 2015;33(29):3356–64.

    Article  Google Scholar 

  6. Bray F, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.

    Article  Google Scholar 

  7. Callahan MK, Postow MA, Wolchok JD. Targeting T cell co-receptors for cancer therapy. Immunity. 2016;44(5):1069–78.

    Article  CAS  Google Scholar 

  8. Larkins E, et al. FDA approval summary: pembrolizumab for the treatment of recurrent or metastatic head and neck squamous cell carcinoma with disease progression on or after platinum-containing chemotherapy. Oncologist. 2017;22(7):873–8.

    Article  CAS  Google Scholar 

  9. Ribas A, et al. Association of pembrolizumab with tumor response and survival among patients with advanced Melanoma. JAMA. 2016;315(15):1600–9.

    Article  CAS  Google Scholar 

  10. Borghaei H, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627–39.

    Article  CAS  Google Scholar 

  11. Fang W, et al. Camrelizumab (SHR-1210) alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma: results from two single-arm, phase 1 trials. Lancet Oncol. 2018;19(10):1338–50.

    Article  CAS  Google Scholar 

  12. Hsu C, et al. Safety and antitumor activity of pembrolizumab in patients with programmed death-ligand 1-positive nasopharyngeal carcinoma: results of the KEYNOTE-028 Study. J Clin Oncol. 2017:JCO2017733675.

  13. Ma BBY, et al. Antitumor activity of nivolumab in recurrent and metastatic nasopharyngeal carcinoma: an international, multicenter study of the Mayo Clinic Phase 2 Consortium (NCI-9742). J Clin Oncol. 2018;36(14):1412–8.

    Article  CAS  Google Scholar 

  14. Cohen EEW, et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2019;393(10167):156–67.

    Article  CAS  Google Scholar 

  15. Saada-Bouzid E, Peyrade F, Guigay J. Immunotherapy in recurrent and or metastatic squamous cell carcinoma of the head and neck. Curr Opin Oncol. 2019;31(3):146–51.

    Article  Google Scholar 

  16. Yen RF, et al. Early restaging whole-body (18)F-FDG PET during induction chemotherapy predicts clinical outcome in patients with locoregionally advanced nasopharyngeal carcinoma. Eur J Nucl Med Mol Imaging. 2005;32(10):1152–9.

    Article  Google Scholar 

  17. Liu WS, et al. The role of pretreatment FDG-PET in nasopharyngeal carcinoma treated with intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2012;82(2):561–6.

    Article  Google Scholar 

  18. Chang KP, et al. Prognostic significance of 18F-FDG PET parameters and plasma Epstein-Barr virus DNA load in patients with nasopharyngeal carcinoma. J Nucl Med. 2012;53(1):21–8.

    Article  CAS  Google Scholar 

  19. Chen R, et al. Relationship between 18F-FDG PET/CT findings and HER2 expression in gastric cancer. J Nucl Med. 2016;57(7):1040–4.

    Article  CAS  Google Scholar 

  20. Lee J, et al. Strong association of epidermal growth factor receptor status with breast cancer FDG uptake. Eur J Nucl Med Mol Imaging. 2017;44(9):1438–47.

    Article  CAS  Google Scholar 

  21. Lv Z, et al. Value of (18)F-FDG PET/CT for predicting EGFR mutations and positive ALK expression in patients with non-small cell lung cancer: a retrospective analysis of 849 Chinese patients. Eur J Nucl Med Mol Imaging. 2018;45(5):735–50.

    Article  CAS  Google Scholar 

  22. Kaira K, et al. 2-Deoxy-2-[fluorine-18] fluoro-d-glucose uptake on positron emission tomography is associated with programmed death ligand-1 expression in patients with pulmonary adenocarcinoma. Eur J Cancer. 2018;101:181–90.

    Article  CAS  Google Scholar 

  23. Chen R, et al. Relationship between the expression of PD-1/PD-L1 and (18)F-FDG uptake in bladder cancer. Eur J Nucl Med Mol Imaging. 2019;46(4):848–54.

    Article  CAS  Google Scholar 

  24. Zhao L, et al. Mismatch repair status and high expression of PD-L1 in nasopharyngeal carcinoma. Cancer Manag Res. 2019;11:1631–40.

    Article  CAS  Google Scholar 

  25. Takada K, et al. Metabolic characteristics of programmed cell death-ligand 1-expressing lung cancer on (18) F-fluorodeoxyglucose positron emission tomography/computed tomography. Cancer Med. 2017;6(11):2552–61.

    Article  CAS  Google Scholar 

  26. Niemeijer AN, et al. Whole body PD-1 and PD-L1 positron emission tomography in patients with non-small-cell lung cancer. Nat Commun. 2018;9(1):4664.

    Article  CAS  Google Scholar 

  27. Hettich M, et al. High-resolution PET imaging with therapeutic antibody-based PD-1/PD-L1 checkpoint tracers. Theranostics. 2016;6(10):1629–40.

    Article  CAS  Google Scholar 

  28. Chang CH, et al. Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell. 2015;162(6):1229–41.

    Article  CAS  Google Scholar 

  29. Mano Y, et al. Correlation between biological marker expression and fluorine-18 fluorodeoxyglucose uptake in hepatocellular carcinoma. Am J Clin Pathol. 2014;142(3):391–7.

    Article  Google Scholar 

  30. Dooms C, et al. Association between 18F-fluoro-2-deoxy-D-glucose uptake values and tumor vitality: prognostic value of positron emission tomography in early-stage non-small cell lung cancer. J Thorac Oncol. 2009;4(7):822–8.

    Article  Google Scholar 

  31. Fang W, et al. EBV-driven LMP1 and IFN-gamma up-regulate PD-L1 in nasopharyngeal carcinoma: implications for oncotargeted therapy. Oncotarget. 2014;5(23):12189–202.

    Article  Google Scholar 

  32. Chen J, et al. Regulation of PD-L1: a novel role of pro-survival signalling in cancer. Ann Oncol. 2016;27(3):409–16.

    Article  CAS  Google Scholar 

  33. Zhou Y, et al. PD-L1 predicts poor prognosis for nasopharyngeal carcinoma irrespective of PD-1 and EBV-DNA load. Sci Rep. 2017;7:43627.

    Article  Google Scholar 

  34. Shitara K, et al. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018;392(10142):123–33.

    Article  CAS  Google Scholar 

  35. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252–64.

    Article  CAS  Google Scholar 

  36. Zhao T, et al. Prognostic value of PD-L1 expression in tumor infiltrating immune cells in cancers: a meta-analysis. PLoS One. 2017;12(4):e0176822.

    Article  Google Scholar 

  37. Chan WK, et al. Prognostic impact of standardized uptake value of F-18 FDG PET/CT in nasopharyngeal carcinoma. Clin Nucl Med. 2011;36(11):1007–11.

    Article  Google Scholar 

  38. Favaro E, et al. Glucose utilization via glycogen phosphorylase sustains proliferation and prevents premature senescence in cancer cells. Cell Metab. 2012;16(6):751–64.

    Article  CAS  Google Scholar 

  39. Hirsch FR, et al. PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project. J Thorac Oncol. 2017;12(2):208–22.

    Article  Google Scholar 

  40. Thompson RH, et al. Costimulatory molecule B7-H1 in primary and metastatic clear cell renal cell carcinoma. Cancer. 2005;104(10):2084–91.

    Article  CAS  Google Scholar 

  41. Xie R, et al. Factors influencing the degradation of archival formalin-fixed paraffin-embedded tissue sections. J Histochem Cytochem. 2011;59(4):356–65.

    Article  CAS  Google Scholar 

  42. Hong L, et al., Spatial and temporal heterogeneity of PD-L1 and its impact on benefit from immune checkpoint blockade in non-small cell lung cancer (NSCLC). J Clin Oncol, 2019. suppl; abstr 9017.

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Funding

This work was funded by the Natural Science Foundation of Fujian Province (Grant number 2016 J01633) and National Natural Science Foundation of China (Grant numbers 81772893 and 81701736).

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Author notes

  1. Liang Zhao, Yanzhen Zhuang and Kaili Fu contributed equally to this work.

Authors and Affiliations

  1. Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China

    Liang Zhao, Kaili Fu, Jianfang Zhuo, Xiyi Liao & Qin Lin

  2. Department of Pathology, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China

    Yanzhen Zhuang, Peiqiong Chen & Yuhuan Wang

  3. Department of Nuclear Medicine & Minnan PET Center, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China

    Haojun Chen

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  1. Liang Zhao
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  2. Yanzhen Zhuang
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Correspondence to Haojun Chen or Qin Lin.

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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. This article does not contain any studies with animals performed by any of the authors.

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Zhao, L., Zhuang, Y., Fu, K. et al. Usefulness of [18F]fluorodeoxyglucose PET/CT for evaluating the PD-L1 status in nasopharyngeal carcinoma. Eur J Nucl Med Mol Imaging 47, 1065–1074 (2020). https://doi.org/10.1007/s00259-019-04654-4

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  • DOI: https://doi.org/10.1007/s00259-019-04654-4

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