Prognostic significance of preoperative metabolic tumour volume and total lesion glycolysis measured by 18F-FDG PET/CT in squamous cell carcinoma of the oral cavity

  • In Sun Ryu
  • Jae Seung Kim
  • Jong-Lyel Roh
  • Kyung-Ja Cho
  • Seung-Ho Choi
  • Soon Yuhl Nam
  • Sang Yoon Kim
Original Article



Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from 18F-FDG PET/CT are emerging prognostic biomarkers in human solid cancers; yet few studies have investigated their clinical and prognostic significance in oral cavity squamous cell carcinoma (OSCC). The present retrospective study evaluated the utility of pretreatment MTV and TLG measured by 18F-FDG PET/CT to predict survival and occult metastasis (OM) in OSCC.


Of 162 patients with OSCC evaluated preoperatively by 18F-FDG PET/CT, 105 who underwent definitive surgery with or without adjuvant therapy were eligible. Maximum standardized uptake value (SUVmax), MTV and TLG were measured. For calculation of MTV, 3-D regions of interest were drawn and a SUV threshold of 2.5 was used for defining regions. Univariate and multivariate analyses identified clinicopathological and imaging variables associated with OM, disease-free survival (DFS) and overall survival (OS).


The median (range) SUVmax, MTV and TLG were 7.3 (0.7–41.9), 4.5 ml (0.7–115.1 ml) and 18.3 g (2.4–224.1 g), respectively. Of 53 patients with clinically negative lymph nodes, OM was detected in 19 (36 %). By univariate and multivariate analyses, MTV (P = 0.018) and TLG (P = 0.011) were both independent predictive factors for OM, although they were not independent of each other. The 4-year DFS and OS rates were 53.0 % and 62.0 %, respectively. Univariate and multivariate analyses revealed that MTV (P = 0.001) and TLG (P = 0.006), with different cut-off levels, were both independent predictive factors for DFS, although they were not independent of each other, and MTV (P = 0.001), TLG (P = 0.002) and the involved resection margin (P = 0.007) were independent predictive factors for OS.


Pretreatment MTV and TLG may be useful in stratifying the likelihood of survival and predicting OM in OSCC.


Oral cavity cancer 18F-FDG PET/CT Metabolic tumour volume Total lesion glycolysis Prognosis 


Conflicts of interest


Grant support

This study was supported by grants (no. 2013-417) from the Asan Institute for Life Science and Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education, Science and Technology (grant no. 2012R1A1A2002039), Seoul, Korea (J.-L. Roh).


  1. 1.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.PubMedCrossRefGoogle Scholar
  2. 2.
    Tankere F, Camproux A, Barry B, Guedon C, Depondt J, Gehanno P. Prognostic value of lymph node involvement in oral cancers: a study of 137 cases. Laryngoscope. 2000;110:2061–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Sano D, Myers JN. Metastasis of squamous cell carcinoma of the oral tongue. Cancer Metastasis Rev. 2007;26:645–62.PubMedCrossRefGoogle Scholar
  4. 4.
    Funk GF, Karnell LH, Robinson RA, Zhen WK, Trask DK, Hoffman HT. Presentation, treatment, and outcome of oral cavity cancer: a National Cancer Data Base report. Head Neck. 2002;24:165–80.PubMedCrossRefGoogle Scholar
  5. 5.
    Roh JL, Cho KJ, Kwon GY, Ryu CH, Chang HW, Choi SH, et al. The prognostic value of hypoxia markers in T2-staged oral tongue cancer. Oral Oncol. 2009;45:63–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Murthy V, Agarwal JP, Laskar SG, Murthy V, Agarwal JP, Laskar SG, et al. Analysis of prognostic factors in 1180 patients with oral cavity primary cancer treated with definitive or adjuvant radiotherapy. J Cancer Res Ther. 2010;6:282–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Allal AS, Slosman DO, Kebdani T, Allaoua M, Lehmann W, Dulguerov P. Prediction of outcome in head-and-neck cancer patients using the standardized uptake value of 2-[18F]fluoro-2-deoxy-D-glucose. Int J Radiat Oncol Biol Phys. 2004;59:1295–300.PubMedCrossRefGoogle Scholar
  8. 8.
    Minn H, Clavo AC, Grenman R, Wahl RL. In vitro comparison of cell proliferation kinetics and uptake of tritiated fluorodeoxyglucose and L-methionine in squamous-cell carcinoma of the head and neck. J Nucl Med. 1995;36:252–8.PubMedGoogle Scholar
  9. 9.
    Haberkorn U, Strauss LG, Reisser C, Haag D, Dimitrakopoulou A, Ziegler S, et al. Glucose uptake, perfusion, and cell proliferation in head and neck tumors: relation of positron emission tomography to flow cytometry. J Nucl Med. 1991;32:1548–55.PubMedGoogle Scholar
  10. 10.
    Menda Y, Graham MM. Update on 18F-fluorodeoxyglucose/positron emission tomography and positron emission tomography/computed tomography imaging of squamous head and neck cancers. Semin Nucl Med. 2005;35:214–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Branstetter BF, Blodgett TM, Zimmer LA, Snyderman CH, Johnson JT, Raman S, et al. Head and neck malignancy: is PET/CT more accurate than PET or CT alone? Radiology. 2005;235:580–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Lonneux M, Hamoir M, Reychler H, Maingon P, Duvillard C, Calais G, et al. Positron emission tomography with [18F]fluorodeoxyglucose improves staging and patient management in patients with head and neck squamous cell carcinoma: a multicenter prospective study. J Clin Oncol. 2010;28:1190–5.PubMedCrossRefGoogle Scholar
  13. 13.
    Quon A, Fischbein NJ, McDougall IR, Le QT, Loo BW, Pinto H, et al. Clinical role of 18F-FDG PET/CT in the management of squamous cell carcinoma of the head and neck and thyroid carcinoma. J Nucl Med. 2007;48:58S–67S.PubMedGoogle Scholar
  14. 14.
    Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50:122S–50S.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Lee P, Weerasuriya DK, Lavori PW, Quon A, Hara W, Maxim PG, et al. Metabolic tumor burden predicts for disease progression and death in lung cancer. Int J Radiat Oncol Biol Phys. 2007;69(2):328–33.PubMedCrossRefGoogle Scholar
  16. 16.
    Chung MK, Jeong HS, Park SG, Jang JY, Son YI, Choi JY, et al. Metabolic tumor volume of [18F]-fluorodeoxyglucose positron emission tomography/computed tomography predicts short-term outcome to radiotherapy with or without chemotherapy in pharyngeal cancer. Clin Cancer Res. 2009;15:5861–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Chen HH, Chiu NT, Su WC, Guo HR, Lee BF. Prognostic value of whole-body total lesion glycolysis at pretreatment FDG PET/CT in non-small cell lung cancer. Radiology. 2012;264:559–66.PubMedCrossRefGoogle Scholar
  18. 18.
    Abd El-Hafez YG, Moustafa HM, Khalil HF, Liao CT, Yen TC. Total lesion glycolysis: a possible new prognostic parameter in oral cavity squamous cell carcinoma. Oral Oncol. 2013;49:261–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Dibble EH, Alvarez AC, Truong MT, Mercier G, Cook EF, Subramaniam RM. 18F-FDG metabolic tumor volume and total glycolytic activity of oral cavity and oropharyngeal squamous cell cancer: adding value to clinical staging. J Nucl Med. 2012;53:709–15.PubMedCrossRefGoogle Scholar
  20. 20.
    Soret M, Bacharach SL, Buvat I. Partial-volume effect in PET tumor imaging. J Nucl Med. 2007;48:932–45.PubMedCrossRefGoogle Scholar
  21. 21.
    Greene FL, Page DL, Fleming ID, Fritz A, Balch CM, Haller DG. AJCC cancer staging manual. 6th ed. New York: Springer; 2002. p. 23–32.CrossRefGoogle Scholar
  22. 22.
    Robbins KT, Shaha AR, Medina JE, Medina J, Sessions R, Shaha A, et al. Consensus statement on the classification and terminology of neck dissection. Arch Otolaryngol Head Neck Surg. 2008;134:536–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefebvre JL, Greiner RH, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004;350(19):1945–52.PubMedCrossRefGoogle Scholar
  24. 24.
    Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004;350:1937–44.PubMedCrossRefGoogle Scholar
  25. 25.
    Shah JP, Cendon RA, Farr HW, Strong EW. Carcinoma of the oral cavity. factors affecting treatment failure at the primary site and neck. Am J Surg. 1976;132:504–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Seol YM, Kwon BR, Song MK, Choi YJ, Shin HJ, Chung JS, et al. Measurement of tumor volume by PET to evaluate prognosis in patients with head and neck cancer treated by chemo-radiation therapy. Acta Oncol. 2010;49:201–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Larson SM, Erdi Y, Akhurst T, Mazumdar M, Macapinlac HA, Finn RD, et al. Tumor treatment response based on visual and quantitative changes in global tumor glycolysis using PET-FDG imaging. The visual response score and the change in total lesion glycolysis. Clin Positron Imaging. 1999;2:159–71.PubMedCrossRefGoogle Scholar
  28. 28.
    Nakamura T, Sumi M. Nodal imaging in the neck: recent advances in US, CT and MR imaging of metastatic nodes. Eur Radiol. 2007;17:1235–41.PubMedCrossRefGoogle Scholar
  29. 29.
    Van den Brekel MW, Stel HV, Castelijns JA, Van der Waal I, Valk J, Meyer CJ, et al. Cervical lymph node metastasis: assessment of radiologic criteria. Radiology. 1990;177:379–84.PubMedGoogle Scholar
  30. 30.
    Romesser PB, Qureshi MM, Shah BA, Chatburn LT, Jalisi S, Devaiah AK. Superior prognostic utility of gross and metabolic tumor volume compared to standardized uptake value using PET/CT in head and neck squamous cell carcinoma patients treated with intensity-modulated radiotherapy. Ann Nucl Med. 2012;26:527–34.PubMedCrossRefGoogle Scholar
  31. 31.
    Allal AS, Dulguerov P, Allaoua M, et al. Standardized uptake value of 2-[(18)F] fluoro-2-deoxy-D-glucose in predicting outcome in head and neck carcinomas treated by radiotherapy with or without chemotherapy. J Clin Oncol. 2002;20:1398–404.PubMedCrossRefGoogle Scholar
  32. 32.
    Machtay M, Natwa M, Andrei J, Hyslop T, Anne PR, Lavarino J, et al. Pretreatment FDG-PET standardized uptake value as a prognostic factor for outcome in head and neck cancer. Head Neck. 2009;31:195–201.PubMedCrossRefGoogle Scholar
  33. 33.
    Minn H, Lapela M, Klemi PJ, Grenman R, Leskinen S, Lindholm P, et al. Prediction of survival with fluorine-18-fluoro-deoxyglucose and PET in head and neck cancer. J Nucl Med. 1997;38:1907–11.PubMedGoogle Scholar
  34. 34.
    Yuen APW, Lam KY, Lam LK, Ho CM, Wong A, Chow TL, et al. Prognostic factors of clinically stage I and II oral tongue carcinoma – a comparative study of stage, thickness, shape, growth pattern, invasive front malignancy grading, Martinez-Gimeno score, and pathologic features. Head Neck. 2002;24:513–20.PubMedCrossRefGoogle Scholar
  35. 35.
    Lim YC, Lee JS, Koo BS, Kim SH, Kim YH, Choi EC. Treatment of contralateral N0 neck in early squamous cell carcinoma of the oral tongue: elective neck dissection versus observation. Laryngoscope. 2006;116:461–5.PubMedCrossRefGoogle Scholar
  36. 36.
    Ferlito A, Silver CE, Rinaldo A. Elective management of the neck in oral cavity squamous carcinoma: current concepts supported by prospective studies. Br J Oral Maxillofac Surg. 2009;47:5–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Thie JA. Understanding the standardized uptake value, its methods, and implications for usage. J Nucl Med. 2004;45:1431–4.PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • In Sun Ryu
    • 1
  • Jae Seung Kim
    • 2
  • Jong-Lyel Roh
    • 1
  • Kyung-Ja Cho
    • 3
  • Seung-Ho Choi
    • 1
  • Soon Yuhl Nam
    • 1
  • Sang Yoon Kim
    • 1
    • 4
  1. 1.Department of Otolaryngology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulSouth Korea
  2. 2.Department of Nuclear Medicine, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulSouth Korea
  3. 3.Department of Pathology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulSouth Korea
  4. 4.Biomedical Research Institute, Korean Institute of Science and TechnologySeoulRepublic of Korea

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