European Radiology

, Volume 27, Issue 5, pp 1912–1921 | Cite as

The role of 18F-fluorodeoxyglucose uptake of bone marrow on PET/CT in predicting clinical outcomes in non-small cell lung cancer patients treated with chemoradiotherapy

  • Jeong Won Lee
  • Ki Hyun Seo
  • Eun-Seog Kim
  • Sang Mi Lee
Nuclear Medicine



This study aimed to assess the relationship between bone marrow (BM) FDG uptake on PET/CT and serum inflammatory markers and to evaluate the prognostic value of BM FDG uptake for predicting clinical outcomes in non-small cell lung cancer (NSCLC) patients.


One hundred and six NSCLC patients who underwent FDG PET/CT for staging work-up and received chemoradiotherapy were enrolled. Mean BM FDG uptake (BM SUV) and BM-to-liver uptake ratio (BLR) were measured, along with volumetric parameters of PET/CT. The relationship of BM SUV and BLR with hematologic parameters and serum inflammatory markers was evaluated. Prognostic values of BM SUV and BLR for predicting progression-free survival (PFS) and overall survival (OS) were assessed.


BM SUV and BLR were significantly correlated with white blood cell count and C-reactive protein level. On univariate analysis, BLR was a significant prognostic factor for both PFS and OS. On multivariate analysis, TNM stage and BLR were independent prognostic factors for PFS, and only TNM stage was an independent prognostic factor for OS.


In NSCLC patients, FDG uptake of BM reflects the systemic inflammatory response and can be used as a biomarker to identify patients with poor prognosis.

Key Points

• Bone marrow FDG uptake is correlated with serum inflammatory markers.

• Bone marrow FDG uptake is an independent prognostic factor for progression-free survival.

• Bone marrow FDG uptake can provide information on predicting lung cancer progression.


Lung cancer Prognosis Positron emission tomography FDG Bone marrow 

Abbreviations and acronyms


Non-small cell lung cancer


Progression-free survival


Overall survival


Neutrophil-to-lymphocyte ratio


Platelet-to-lymphocyte ratio


C-reactive protein




Standardized uptake value


Bone marrow


Maximum SUV of tumour


Metabolic tumour volume


Total lesion glycolysis


Bone marrow-to-liver uptake ratio of SUV


White blood cell



This work was supported in part by the Soonchunhyang University Research Fund, and by the research fund of Catholic Kwandong University International St. Mary’s Hospital (CKURF-201601650001). The scientific guarantor of this publication is Sang Mi Lee, M.D., Ph.D. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. The authors state that this work has not received any funding. No complex statistical methods were necessary for this paper. Institutional Review Board approval was obtained. Written informed consent was waived by the Institutional Review Board. Methodology: Retrospective prognostic study performed at one institution


  1. 1.
    Ettinger DS, Akerley W, Bepler G et al (2010) Non-small cell lung cancer. J Natl Compr Canc Netw 8:740–801PubMedGoogle Scholar
  2. 2.
    Ahn JS, Ahn YC, Kim JH et al (2015) Multinational randomized phase III trial with or without consolidation chemotherapy using docetaxel and cisplatin after concurrent chemoradiation in inoperable stage III non-small-cell lung cancer: KCSG-LU05-04. J Clin Oncol 33:2660–2666CrossRefPubMedGoogle Scholar
  3. 3.
    Romero-Ventosa EY, Blanco-Prieto S, Gonzalez-Pineiro AL, Rodriguez-Berrocal FJ, Pineiro-Corrales G, Paez de la Cadena M (2015) Pretreatment levels of the serum biomarkers CEA, CYFRA 21-1, SCC and the soluble EGFR and its ligands EGF, TGF-alpha, HB-EGF in the prediction of outcome in erlotinib treated non-small-cell lung cancer patients. Springerplus 4:171CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Sun H, Hu P, Shen H et al (2015) Albumin and neutrophil combined prognostic grade as a new prognostic factor in non-small cell lung cancer: results from a large consecutive cohort. PLoS One 10:e0144663Google Scholar
  5. 5.
    Pistelli M, De Lisa M, Ballatore Z et al (2015) Pre-treatment neutrophil to lymphocyte ratio may be a useful tool in predicting survival in early triple negative breast cancer patients. BMC Cancer 15:195CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Hsu JT, Liao CK, Le PH et al (2015) Prognostic value of the preoperative neutrophil to lymphocyte ratio in resectable gastric cancer. Medicine (Baltimore) 94:e1589Google Scholar
  7. 7.
    Wu G, Yao Y, Bai C et al (2015) Combination of platelet to lymphocyte ratio and neutrophil to lymphocyte ratio is a useful prognostic factor in advanced non-small cell lung cancer patients. Thorac Cancer 6:275–287CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Takahashi Y, Horio H, Hato T et al (2015) Prognostic significance of preoperative neutrophil-lymphocyte ratios in patients with stage I non-small cell lung cancer after complete resection. Ann Surg Oncol Suppl 3:1324–1331CrossRefGoogle Scholar
  9. 9.
    Tolia M, Tsoukalas N, Kyrgias G et al (2015) Prognostic significance of serum inflammatory response markers in newly diagnosed non-small cell lung cancer before chemoirradiation. Biomed Res Int 2015:485732Google Scholar
  10. 10.
    Jimenez-Bonilla JF, Quirce R, Martinez-Rodriguez I et al (2013) Diagnosis of recurrence and assessment of post-recurrence survival in patients with extracranial non-small cell lung cancer evaluated by 18F-FDG PET/CT. Lung Cancer 81:71–76CrossRefPubMedGoogle Scholar
  11. 11.
    Lee AY, Choi SJ, Jung KP, Park JS, Lee SM, Bae SK (2014) Characteristics of metastatic mediastinal lymph nodes of non-small cell lung cancer on preoperative F-18 FDG PET/CT. Nucl Med Mol Imaging 48:41–46CrossRefPubMedGoogle Scholar
  12. 12.
    Lee JW, Lee SM, Yun M, Cho A (2016) Prognostic value of volumetric parameters on staging and posttreatment FDG PET/CT in patients with stage IV non-small cell lung cancer. Clin Nucl Med 41:347–353CrossRefPubMedGoogle Scholar
  13. 13.
    Im HJ, Pak K, Cheon GJ et al (2015) 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 42:241–251CrossRefPubMedGoogle Scholar
  14. 14.
    Bural GG, Torigian DA, Chen W, Houseni M, Basu S, Alavi A (2010) Increased 18F-FDG uptake within the reticuloendothelial system in patients with active lung cancer on PET imaging may indicate activation of the systemic immune response. Hell J Nucl Med 13:23–25PubMedGoogle Scholar
  15. 15.
    Van de Wiele C, VandeVyver F, Debruyne C, Philippe J, van Meerbeeck JP (2008) FDG uptake by the bone marrow in NSCLC patients is related to TGF-beta but not to VEGF or G-CSF serum levels. Eur J Nucl Med Mol Imaging 35:519–522CrossRefPubMedGoogle Scholar
  16. 16.
    Prevost S, Boucher L, Larivee P, Boileau R, Benard F (2006) Bone marrow hypermetabolism on 18F-FDG PET as a survival prognostic factor in non-small cell lung cancer. J Nucl Med 47:559–565PubMedGoogle Scholar
  17. 17.
    Mittal V, El Rayes T, Narula N, McGraw TE, Altorki NK, Barcellos-Hoff MH (2016) The microenvironment of lung cancer and therapeutic implications. Adv Exp Med Biol 890:75–110CrossRefPubMedGoogle Scholar
  18. 18.
    Delbeke D, Coleman RE, Guiberteau MJ et al (2006) Procedure guideline for tumor imaging with 18F-FDG PET/CT 1.0. J Nucl Med 47:885–895PubMedGoogle Scholar
  19. 19.
    Murata Y, Kubota K, Yukihiro M, Ito K, Watanabe H, Shibuya H (2006) Correlations between 18F-FDG uptake by bone marrow and hematological parameters: measurements by PET/CT. Nucl Med Biol 33:999–1004CrossRefPubMedGoogle Scholar
  20. 20.
    Inoue K, Goto R, Okada K, Kinomura S, Fukuda H (2009) A bone marrow F-18 FDG uptake exceeding the liver uptake may indicate bone marrow hyperactivity. Ann Nucl Med 23:643–649CrossRefPubMedGoogle Scholar
  21. 21.
    Nunez R, Rini JN, Tronco GG, Tomas MB, Nichols K, Palestro CJ (2005) Correlation of hematologic parameters with bone marrow and spleen uptake in FDG PET. Rev Esp Med Nucl 24:107–112CrossRefPubMedGoogle Scholar
  22. 22.
    Leimgruber A, Moller A, Everitt SJ et al (2014) Effect of platinum-based chemoradiotherapy on cellular proliferation in bone marrow and spleen, estimated by (18)F-FLT PET/CT in patients with locally advanced non-small cell lung cancer. J Nucl Med 55:1075–1080CrossRefPubMedGoogle Scholar
  23. 23.
    Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454:436–444CrossRefPubMedGoogle Scholar
  24. 24.
    Kundu JK, Surh YJ (2008) Inflammation: gearing the journey to cancer. Mutat Res 659:15–30CrossRefPubMedGoogle Scholar
  25. 25.
    O'Dowd C, McRae LA, McMillan DC, Kirk A, Milroy R (2010) Elevated preoperative C-reactive protein predicts poor cancer specific survival in patients undergoing resection for non-small cell lung cancer. J Thorac Oncol 5:988–992CrossRefPubMedGoogle Scholar
  26. 26.
    Yeun JY, Kaysen GA (1998) Factors influencing serum albumin in dialysis patients. Am J Kidney Dis 32:S118–S125CrossRefPubMedGoogle Scholar
  27. 27.
    Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140:883–899CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Hyun SH, Ahn HK, Ahn MJ et al (2015) Volume-based assessment with 18F-FDG PET/CT improves outcome prediction for patients with stage IIIA-N2 non-small cell lung cancer. AJR Am J Roentgenol 205:623–628CrossRefPubMedGoogle Scholar
  29. 29.
    Huang W, Fan M, Liu B et al (2014) Value of metabolic tumor volume on repeated 18F-FDG PET/CT for early prediction of survival in locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy. J Nucl Med 55:1584–1590CrossRefPubMedGoogle Scholar
  30. 30.
    Vera P, Mezzani-Saillard S, Edet-Sanson A et al (2014) FDG PET during radiochemotherapy is predictive of outcome at 1 year in non-small-cell lung cancer patients: a prospective multicentre study (RTEP2). Eur J Nucl Med Mol Imaging 41:1057–1065CrossRefPubMedGoogle Scholar
  31. 31.
    Blodgett TM, Ames JT, Torok FS, McCook BM, Meltzer CC (2004) Diffuse bone marrow uptake on whole-body F-18 fluorodeoxyglucose positron emission tomography in a patient taking recombinant erythropoietin. Clin Nucl Med 29:161–163CrossRefPubMedGoogle Scholar

Copyright information

© European Society of Radiology 2016

Authors and Affiliations

  • Jeong Won Lee
    • 1
    • 2
  • Ki Hyun Seo
    • 3
  • Eun-Seog Kim
    • 4
  • Sang Mi Lee
    • 5
  1. 1.Department of Nuclear MedicineCatholic Kwandong University College of Medicine, International St. Mary’s HospitalIncheonKorea
  2. 2.Institute for Integrative MedicineCatholic Kwandong University College of Medicine, International St. Mary’s HospitalIncheonKorea
  3. 3.Division of Pulmonary Medicine, Department of Internal MedicineSoonchunhyang University Cheonan HospitalCheonanKorea
  4. 4.Department of Radiation OncologySoonchunhyang University Cheonan HospitalCheonanKorea
  5. 5.Department of Nuclear MedicineSoonchunhyang University Cheonan HospitalCheonanKorea

Personalised recommendations